Reaction #1583883

Reaction equation

3-methyl-1-phenylethylpyrrolidin-3-ol

(R)-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid

(R)-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid

DIPEA

oxalyl chloride

→

(4S)-3-(3-methyl-1-phenylethylpyrrolidin-3-yl) 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Yield 48.0%

Solvents

dichloromethane

dichloromethane

DMF

Conditions

Workup

1. 1
   Otherwas synthesized
2. 2
   OtherThe reaction was conducted at 25° C. until the completion of reaction
3. 3
   OtherThe resulting mixture was evaporated under reduced pressure
4. 4
   Otherto remove oxalyl chloride
5. 5
   Temperatureunder cooling in an ice bath respectively
6. 6
   Otherwas conducted at 25° C
7. 7
   OtherAfter the completion of reaction
8. 8
   Washthe reaction solution was washed with water thrice
9. 9
   DryingThe organic phase was dried over sodium sulfate
10. 10
    Filtrationfiltered by suction
11. 11
    OtherThe filtrate was evaporated to dryness
12. 12
    Otherpurified by column chromatography (silica gel column, eluted with petroleum ether:ethyl acetate=78:1 (volumetric ratio))

Procedure

According to Example 15, (R)-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid was synthesized. To a solution of (R)-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid (2.9 g, 8.73 mmol) in dichloromethane was added 0.1 mL DMF. To the mixture was slowly added oxalyl chloride (2.2 g, 17.33 mmol) dropwisely in an ice bath. The reaction was conducted at 25° C. until the completion of reaction. The resulting mixture was evaporated under reduced pressure to remove oxalyl chloride. To the reaction flask were slowly added dichloromethane (20 mL), 3-methyl-1-phenylethylpyrrolidin-3-ol (1 g, 4.87 mmol) and DIPEA (1.56 g, 12.1 mmol) dropwisely under cooling in an ice bath respectively and successively. The reaction was conducted at 25° C. After the completion of reaction monitored by HPLC, the reaction solution was washed with water thrice. The organic phase was dried over sodium sulfate, and filtered by suction. The filtrate was evaporated to dryness, and purified by column chromatography (silica gel column, eluted with petroleum ether:ethyl acetate=78:1 (volumetric ratio)) to produce (4S)-3-(3-methyl-1-phenylethylpyrrolidin-3-yl) 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate (1.21 g) in a yield of 48%.

Source