Sodium triacetoxyborohydride → (+/-)-(3R,4R)-benzyl 3-((1-(5-benzyl-2-(2,5-difluorophenyl)oxazol-4-yl)-2,2-dimethylpropylamino)methyl)-4-fluoropyrrolidine-1-carboxylate

HRID 404852노트

반응식

HRID 404852 반응식
[CH2:1]([C:8]1[O:12][C:11]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[F:20])=[N:10][C:9]=1[CH:21]([NH2:26])[C:22]([CH3:25])([CH3:24])[CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[F:41][C@@H:42]1[C@H:46]([CH:47]=O)[CH2:45][N:44]([C:49]([O:51][CH2:52][C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)=[O:50])[CH2:43]1>C(Cl)Cl>[CH2:1]([C:8]1[O:12][C:11]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[F:20])=[N:10][C:9]=1[CH:21]([NH:26][CH2:47][C@H:46]1[C@@H:42]([F:41])[CH2:43][N:44]([C:49]([O:51][CH2:52][C:53]2[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=2)=[O:50])[CH2:45]1)[C:22]([CH3:23])([CH3:25])[CH3:24])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

5

반응물 3

HCID 5049666Sodium triacetoxyborohydrideHCID 53482935(3R,4S)-benzyl 3-fluoro-4-formylpyrrolidine-1-carboxylateHCID 67449935(+/-)-1-(5-Benzyl-2-(2,5-difluorophenyl)oxazol-4-yl)-2,2-dimethylpropan-1-amine

생성물 1

HCID 86693896(+/-)-(3R,4R)-benzyl 3-((1-(5-benzyl-2-(2,5-difluorophenyl)oxazol-4-yl)-2,2-dimethylpropylamino)methyl)-4-fluoropyrrolidine-1-carboxylate수율 9.2%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of (±)-1-(5-benzyl-2-(2,5-difluorophenyl)oxazol-4-yl)-2,2-dimethylpropan-1-amine (240 mg, 0.673 mmol) in CH2Cl2 (5.0 mL) was added NaBH(OAc)3 (2.86 g, 13.5 mmol). To this solution, the crude (3R,4S)-benzyl 3-fluoro-4-formylpyrrolidine-1-carboxylate (obtained from 2.0 equiv. of (3R,4R)-benzyl 3-fluoro-4-vinylpyrrolidine-1-carboxylate) in CH2Cl2 (1.0 mL) was rapidly added at room temperature. After stirred for 20 min, the reaction mixture was quenched with saturated NaHCO3 solution and extracted with EtOAc. The organic layer was washed with water and brine, dried over anhydrous Na2SO4, filtered and concentrated. The crude product was purified on preparative reverse phase HPLC. The combined fractions of the product were neutralized with saturated NaHCO3 solution, which was then extracted with EtOAc. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to yield (±)-(3R,4R)-benzyl 3-((1-(5-benzyl-2-(2,5-difluorophenyl)oxazol-4-yl)-2,2-dimethylpropylamino)methyl)-4-fluoropyrrolidine-1-carboxylate (37 mg, 9.2%). LC/MS (uplc) MH+ 592.4, 0.91 min.

후처리

  1. customthe reaction mixture was quenched with saturated NaHCO3 solution
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified on preparative reverse phase HPLC
  8. extractionwas then extracted with EtOAc
  9. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-af0406b55c1c41e3b141fb4f560e3c01
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08748626B2

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