111011-78-0

Basic information

• Product Name: 3-(5,5-diMethyl-2-oxo-1,3,2-dioxaphorinane-2-yl)-4-(3-nitrophenyl)-bu-3-en-2-one
• Synonyms: 3-(5,5-diMethyl-2-oxo-1,3,2-dioxaphorinane-2-yl)-4-(3-nitrophenyl)-bu-3-en-2-one;5,5-DiMethyl-2-(1-(3-nitrophenyl)-3-oxo-1-buten-2-yl)-2-oxo-1,3,2-dioxaphosphorinane;3-(5,5-Dimethyl-2-oxido-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-3-buten-2-one;(Z)-3-(5,5-Dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)-4-(3-nitrophenyl)but-3-en-2-one;(Z)-3-(5,5-dimethyl-2-oxo-1,3,2λ5-dioxaphosphinan-2-yl)-4-(3-nitrophenyl)but-3-en-2-one
• CAS NO: 111011-78-0
• Molecular Formula: C₁₅H₁₈NO₆P
• Molecular Weight: 339.280281
• Mol File: 111011-78-0.mol
• Article Data: 2

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 3-(5,5-diMethyl-2-oxo-1,3,2-dioxaphorinane-2-yl)-4-(3-nitrophenyl)-bu-3-en-2-one(CAS DataBase Reference)
• NIST Chemistry Reference: 3-(5,5-diMethyl-2-oxo-1,3,2-dioxaphorinane-2-yl)-4-(3-nitrophenyl)-bu-3-en-2-one(111011-78-0)
• EPA Substance Registry System: 3-(5,5-diMethyl-2-oxo-1,3,2-dioxaphorinane-2-yl)-4-(3-nitrophenyl)-bu-3-en-2-one(111011-78-0)

Safety Data

• Hazardous Substances Data: 111011-78-0(Hazardous Substances Data)

Usage

Description

3-(5,5-dimethyl-2-oxo-1,3,2-dioxaphorinane-2-yl)-4-(3-nitrophenyl)-but-3-en-2-one is a complex organic chemical compound characterized by the presence of a dioxaphorinane ring, a nitrophenyl group, and a butenone moiety. 3-(5,5-diMethyl-2-oxo-1,3,2-dioxaphorinane-2-yl)-4-(3-nitrophenyl)-bu-3-en-2-one is highly reactive and serves as a versatile building block in organic synthesis, making it a promising candidate for various applications across different industries.

Uses

Used in Pharmaceutical Industry:
3-(5,5-dimethyl-2-oxo-1,3,2-dioxaphorinane-2-yl)-4-(3-nitrophenyl)-but-3-en-2-one is used as a key intermediate in the synthesis of pharmaceutical compounds for its unique reactivity and structural features. Its potential applications include the development of new drugs with improved efficacy and selectivity.
Used in Agrochemical Industry:
In the agrochemical sector, 3-(5,5-dimethyl-2-oxo-1,3,2-dioxaphorinane-2-yl)-4-(3-nitrophenyl)-but-3-en-2-one is utilized as a precursor in the production of agrochemicals, such as pesticides and herbicides. Its unique structure and reactivity contribute to the development of novel and effective agrochemicals with reduced environmental impact.
Used in Material Science:
3-(5,5-dimethyl-2-oxo-1,3,2-dioxaphorinane-2-yl)-4-(3-nitrophenyl)-but-3-en-2-one is employed as a building block in the synthesis of advanced materials with specific properties. Its incorporation into polymers, coatings, and other materials can lead to the development of innovative products with improved performance and functionality.
Used in Organic Chemistry Research:
Due to its unique structure and reactivity, 3-(5,5-dimethyl-2-oxo-1,3,2-dioxaphorinane-2-yl)-4-(3-nitrophenyl)-but-3-en-2-one is of significant interest for further research and development in the field of organic chemistry. It serves as a valuable tool for exploring new synthetic pathways, understanding reaction mechanisms, and discovering novel chemical transformations.

Synthetic route

3-(dimorpholinomethyl)-1-nitrobenzene (40891-03-0) + 2-acetonyl-5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinane (111011-80-4) → 5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0)

Conditions	Yield
With trifluoroacetic acid In toluene 1.) 60 deg C, 30 min, 2.) 0-10 deg C, 3 h;	93%
With trifluoroacetic acid In toluene for 2.5h; Ambient temperature;	93.2%

3-nitro-benzaldehyde (99-61-6) + 2-acetonyl-5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinane (111011-80-4) → 5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0)

Conditions	Yield
With piperidine; acetic acid In benzene for 6.5h; Heating;	31%

2-methoxy-5,5-dimethyl-1,3,2-dioxaphosphorinane (1005-69-2) → 5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 65.8 percent / diethyl ether / 7 h / Heating 2: 31 percent / piperidine, acetic acid / benzene / 6.5 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 65.8 percent / diethyl ether / 7 h / Heating 2: 93.2 percent / trifluoroacetic acid / toluene / 2.5 h / Ambient temperature View Scheme

2,2-Dimethyl-1,3-propanediol (126-30-7) + chromic acid → 5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 33 percent / 100 °C 2: 65.8 percent / diethyl ether / 7 h / Heating 3: 31 percent / piperidine, acetic acid / benzene / 6.5 h / Heating View Scheme
Multi-step reaction with 3 steps 1: 33 percent / 100 °C 2: 65.8 percent / diethyl ether / 7 h / Heating 3: 93.2 percent / trifluoroacetic acid / toluene / 2.5 h / Ambient temperature View Scheme

(E)-3-Amino-but-2-enoic acid 1-benzyl-piperidin-3-yl ester + 5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) → 5-(5,5-Dimethyl-2-oxo-2λ5-[1,3,2]dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid 1-benzyl-piperidin-3-yl ester

Conditions	Yield
In toluene Heating;	74%

5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) + C18(13)CH22N2O2 → 2-(N-benzyl-N-phenylamino)ethyl 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2-<(13)C>methyl-6-methyl-4-(3-nitrophenyl)pyridine-3-carboxylate

Conditions	Yield
In isopropyl alcohol for 2h; Heating;	74%

(E)-3-Amino-but-2-enoic acid 2-{4-[bis-(4-fluoro-phenyl)-methyl]-piperazin-1-yl}-ethyl ester + 5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) → 5-(5,5-Dimethyl-2-oxo-2λ5-[1,3,2]dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid 2-{4-[bis-(4-fluoro-phenyl)-methyl]-piperazin-1-yl}-ethyl ester

Conditions	Yield
In toluene Heating;	62%

(E)-3-Amino-but-2-enoic acid 6-(benzyl-methyl-amino)-hexyl ester + 5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) → 5-(5,5-Dimethyl-2-oxo-2λ5-[1,3,2]dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid 6-(benzyl-methyl-amino)-hexyl ester

Conditions	Yield
In toluene Heating;	61%

2-ethyl 3-aminocrotonate (54527-73-0) + 5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) → 2-(N-benzyl-N-methylamino)ethyl 2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate (98908-19-1)

Conditions	Yield
In toluene Heating;	60%

(E)-3-Amino-but-2-enoic acid 2-[4-(3-phenyl-propyl)-piperazin-1-yl]-ethyl ester + 5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) → 5-(5,5-Dimethyl-2-oxo-2λ5-[1,3,2]dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid 2-[4-(3-phenyl-propyl)-piperazin-1-yl]-ethyl ester

Conditions	Yield
In toluene Heating;	44%

(E)-3-Amino-but-2-enoic acid 2-dibenzylamino-ethyl ester + 5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) → 5-(5,5-Dimethyl-2-oxo-2λ5-[1,3,2]dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid 2-dibenzylamino-ethyl ester

Conditions	Yield
In toluene Heating;	40%

5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) + methyl 3-aminocrotonate (14205-39-1) → methyl 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate (102097-81-4)

Conditions	Yield
In toluene for 15h; Heating;	40%

isopropyl 3-aminocrotonate (14205-46-0) + 5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) → 5-(5,5-Dimethyl-2-oxo-2λ5-[1,3,2]dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid isopropyl ester

Conditions	Yield
In toluene Heating;	38%

(S)-2-methoxy-2-phenylethyl 3-aminocrotonate + 5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) → (2S)-2-methoxy-2-phenylethyl (4R)-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate (128194-08-1) + (2S)-2-methoxy-2-phenylethyl (4S)-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate (128194-07-0)

Conditions	Yield
In toluene for 3h; Heating;	A n/a B 37%

3-aminobut-2-enoic acid octyl ester (27618-18-4) + 5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) → 5-(5,5-Dimethyl-2-oxo-2λ5-[1,3,2]dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid octyl ester

Conditions	Yield
In toluene Heating;	36%

(E)-3-Amino-but-2-enoic acid 2-(benzo[1,3]dioxol-5-ylmethyl-methyl-amino)-ethyl ester + 5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) → 5-(5,5-Dimethyl-2-oxo-2λ5-[1,3,2]dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid 2-(benzo[1,3]dioxol-5-ylmethyl-methyl-amino)-ethyl ester

Conditions	Yield
In toluene Heating;	35%

methyl 3-(N-ethylamino)crotonate (3814-11-7) + 5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) → 5-(5,5-Dimethyl-2-oxo-2λ5-[1,3,2]dioxaphosphinan-2-yl)-1-ethyl-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid methyl ester (117949-74-3)

Conditions	Yield
In acetonitrile Heating;	33%

β-Aminocrotonic acid dodecyl ester (43107-10-4) + 5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) → 5-(5,5-Dimethyl-2-oxo-2λ5-[1,3,2]dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid dodecyl ester

Conditions	Yield
In toluene Heating;	30%

5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) → (-)-Efonidipine

Conditions	Yield
Multi-step reaction with 4 steps 1: toluene / 3 h / Heating 2: 1.) NaH / 1.) THF, 0 deg C, 30 min, 2.) THF, RT, 30 min 3: 1.) NaH / 1.) DMSO, RT, 20 min, 2.) DMSO, benzene, RT, 30 min 4: 28percent HCl-EtOH / 1.5 h / Ambient temperature View Scheme

5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) → (+)-Efonidipine

Conditions	Yield
Multi-step reaction with 4 steps 1: 37 percent / toluene / 3 h / Heating 2: 1.) NaH / 1.) THF, 0 deg C, 30 min, 2.) THF, RT, 30 min 3: 1.) NaH / 1.) DMSO, RT, 20 min, 2.) DMSO, benzene, RT, 30 min 4: 1.14 g / 28percent HCl-EtOH / 1.5 h / Ambient temperature View Scheme

5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) → (R)-5-(5,5-Dimethyl-2-oxo-2λ5-[1,3,2]dioxaphosphinan-2-yl)-1-methoxymethyl-2,6-dimethyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3-carboxylic acid 2-(benzyl-phenyl-amino)-ethyl ester

Conditions	Yield
Multi-step reaction with 3 steps 1: toluene / 3 h / Heating 2: 1.) NaH / 1.) THF, 0 deg C, 30 min, 2.) THF, RT, 30 min 3: 1.) NaH / 1.) DMSO, RT, 20 min, 2.) DMSO, benzene, RT, 30 min View Scheme

5,5-dimethyl-2-<1-(3-nitrophenyl)-3-oxo-1-buten-2-yl>-2-oxo-1,3,2-dioxaphosphorinane (111011-78-0) → (S)-2-ethyl 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-1-methoxymethyl-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate (128194-11-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 37 percent / toluene / 3 h / Heating 2: 1.) NaH / 1.) THF, 0 deg C, 30 min, 2.) THF, RT, 30 min 3: 1.) NaH / 1.) DMSO, RT, 20 min, 2.) DMSO, benzene, RT, 30 min View Scheme

Upstream product

• 126-30-7 2,2-Dimethyl-1,3-propanediol 
• 1005-69-2 2-methoxy-5,5-dimethyl-1,3,2-dioxaphosphorinane 
• 40891-03-0 3-(dimorpholinomethyl)-1-nitrobenzene 
• 111011-80-4 2-acetonyl-5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinane 
• 99-61-6 3-nitro-benzaldehyde 

Downstream Products

• 128194-09-2 (2S)-2-methoxy-2-phenylethyl (4S)-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-1-methoxymethyl-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate 
• 128194-11-6 (S)-2-ethyl 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-1-methoxymethyl-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate 
• 102097-81-4 methyl 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate 
• 128194-08-1 (2S)-2-methoxy-2-phenylethyl (4R)-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate 
• 128194-07-0 (2S)-2-methoxy-2-phenylethyl (4S)-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate 
• 111011-63-3 efonidipine 
• 98908-19-1 2-(N-benzyl-N-methylamino)ethyl 2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate 

Relevant articles and documents

Synthesis of 1,4-dihydropyridine-5-phosphonates and their calcium-antagonistic and antihypertensive activities

The effect of the 3-carboxylic-ester variation in 2,2-dimethyltrimethylene 3-alkoxycarbonyl-4-aryl-1,4-dihydro-2,6-dimethyl-5-pyridinephosphonate s (1) was investigated with relation to the calcium-antagonistic and antihypertensive activities: the analogs containing the alkyl groups of not more than 12 carbons and an amino functionality in the carboxylic-ester moiety were synthesized to be examined for biological activities. Among them, 2-[benzyl(phenyl)amino]-ethyl 5-(5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydro-2,6-di methyl-4-(3-nitrophenyl)-3-pyridine-carboxylate hydrochloride ethanol (NZ-105) showed particularly beneficial activities and was selected for further pharmacological studies and clinical development. Some aspects of the structure-activity relationships and solid-state structure of NZ-105 by X-ray crystallographic analysis were described.