4-Methylmorpholine → (3S,5R)-5-Biphenyl-4-ylmethyl-3-hydroxymethyl-3-methyl-pyrrolidin-2-one

HRID 1855315노트

반응식

HRID 1855315 반응식
[C:1]1([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:6]=[CH:5][C:4]([CH2:7][C@H:8]2[NH:12][C:11](=[O:13])[C@:10]([CH3:17])([C:14](O)=[O:15])[CH2:9]2)=[CH:3][CH:2]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+]>O.C1COCC1>[C:1]1([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:2]=[CH:3][C:4]([CH2:7][C@H:8]2[NH:12][C:11](=[O:13])[C@@:10]([CH2:14][OH:15])([CH3:17])[CH2:9]2)=[CH:5][CH:6]=1

참가 물질

7

반응물 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 66739144(3R,5R)-5-Biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-3-carboxylic acid

생성물 1

HCID 68189790(3S,5R)-5-Biphenyl-4-ylmethyl-3-hydroxymethyl-3-methyl-pyrrolidin-2-one수율 98%

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

(3R,5R)-5-Biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-3-carboxylic acid (25.0 g, 80.8 mmol) was combined with THF (500 mL) and NMM (25 mL, 230 mmol). The resulting mixture was cooled at 0° C. (jacket temp set at −5° C.) and isobutyl chloroformate (21.0 mL, 162 mmol) was added dropwise via addition funnel, while maintaining the internal temperature below 5° C.). The mixture was stirred at 0° C. for 20 minutes. Sodium borohydride (12.2 g, 323 mmol) dissolved in water (40 mL) was added dropwise and the mixture was stirred at 0° C. for 20 minutes (>98% conversion). The reaction was quenched with 1M aqueous HCl (300 mL) and the mixture was stirred at room temperature for 1 hour. Most of solvent was distilled off, leaving a white slurry. The slurry was stirred for 60 minutes and then filtered (small particles, slow filtration) to yield the title compound as a white solid (23 g; >98% purity).

후처리

  1. additionwas added dropwise via addition funnel
  2. temperaturewhile maintaining the internal temperature below 5° C.)
  3. additionwas added dropwise
  4. stirringthe mixture was stirred at 0° C. for 20 minutes (>98% conversion)
  5. customThe reaction was quenched with 1M aqueous HCl (300 mL)
  6. stirringthe mixture was stirred at room temperature for 1 hour
  7. distillationMost of solvent was distilled off
  8. customleaving a white slurry
  9. stirringThe slurry was stirred for 60 minutes
  10. filtrationfiltered
  11. filtration(small particles, slow filtration)

출처 및 근거

ORD 기록
ord-bc866303c4ce4f79944a7f18df0f6ff7
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08962864B2

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