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

HRID 1496701Notes

Reaction equation

HRID 1496701 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C@H:6]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([N+:22]([O-:24])=[O:23])[CH:17]=2)[C:7]([C:13](O)=[O:14])=[C:8]([CH3:12])[NH:9][C:10]=1[CH3:11])=[O:4].C(Cl)(=O)C(Cl)=O.[CH3:31][C:32]1([OH:45])[CH2:36][CH2:35][N:34]([CH:37]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH3:38])[CH2:33]1.CCN(C(C)C)C(C)C>ClCCl.CN(C=O)C>[CH3:12][C:8]1[NH:9][C:10]([CH3:11])=[C:5]([C:3]([O:2][CH3:1])=[O:4])[C@H:6]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([N+:22]([O-:24])=[O:23])[CH:17]=2)[C:7]=1[C:13]([O:45][C:32]1([CH3:31])[CH2:36][CH2:35][N:34]([CH:37]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH3:38])[CH2:33]1)=[O:14]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 748472(4R)-5-(Methoxycarbonyl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid2×HCID 899616513-Methyl-1-phenylethylpyrrolidin-3-ol

Product 1

HCID 89961723(4S)-3-(3-methyl-1-phenylethylpyrrolidin-3-yl) 5-methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylateYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

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%.

Workup

  1. customwas synthesized
  2. customThe reaction was conducted at 25° C. until the completion of reaction
  3. customThe resulting mixture was evaporated under reduced pressure
  4. customto remove oxalyl chloride
  5. temperatureunder cooling in an ice bath respectively
  6. customwas conducted at 25° C
  7. customAfter the completion of reaction
  8. washthe reaction solution was washed with water thrice
  9. dry with materialThe organic phase was dried over sodium sulfate
  10. filtrationfiltered by suction
  11. customThe filtrate was evaporated to dryness
  12. custompurified by column chromatography (silica gel column, eluted with petroleum ether:ethyl acetate=78:1 (volumetric ratio))

Sources & evidence

ORD record
ord-ca2cfbe06f644e20875f61d9931576a9
Source dataset
uspto-grants-2015_12
Patent number
US09198902B2

Reaction notes

Loading…