反応 #1583883

ord-ca2cfbe06f644e20875f61d9931576a9

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    その他was synthesized
  2. 2
    その他The reaction was conducted at 25° C. until the completion of reaction
  3. 3
    その他The resulting mixture was evaporated under reduced pressure
  4. 4
    その他to remove oxalyl chloride
  5. 5
    温度under cooling in an ice bath respectively
  6. 6
    その他was conducted at 25° C
  7. 7
    その他After the completion of reaction
  8. 8
    洗浄the reaction solution was washed with water thrice
  9. 9
    乾燥The organic phase was dried over sodium sulfate
  10. 10
    ろ過filtered by suction
  11. 11
    その他The filtrate was evaporated to dryness
  12. 12
    その他purified by column chromatography (silica gel column, eluted with petroleum ether:ethyl acetate=78:1 (volumetric ratio))

実験手順

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%.

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US09198902B2uspto-grants-2015_12