Bromoacetonitrile → 1-(1,1-Dimethylethyl) 2-methyl (2R,5R)-2-(cyanomethyl)-5-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-1,2-pyrrolidinedicarboxylate

HRID 1717208노트

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HRID 1717208 반응식
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([C@@H:16]2[N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@H:19]([C:28]([O:30][CH3:31])=[O:29])[CH2:18][CH2:17]2)=[CH:12][CH:11]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.Br[CH2:43][C:44]#[N:45]>C1COCC1>[C:44]([CH2:43][C@@:19]1([C:28]([O:30][CH3:31])=[O:29])[CH2:18][CH2:17][C@H:16]([C:13]2[CH:12]=[CH:11][C:10]([O:9][CH2:8][C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[F:1])=[CH:15][CH:14]=2)[N:20]1[C:21]([O:23][C:24]([CH3:26])([CH3:27])[CH3:25])=[O:22])#[N:45]

참가 물질

5

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HCID 11534BromoacetonitrileHCID 2733832Lithium HexamethyldisilazideHCID 594689471-(1,1-Dimethylethyl) 2-methyl (2S,5R)-5-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-1,2-pyrrolidinedicarboxylate

생성물 1

HCID 594689751-(1,1-Dimethylethyl) 2-methyl (2R,5R)-2-(cyanomethyl)-5-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-1,2-pyrrolidinedicarboxylate

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

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온도
-35 °C

실험 절차

To a solution of 1-(1,1-dimethylethyl) 2-methyl (2S,5R)-5-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-1,2-pyrrolidinedicarboxylate (D34, 45 g) in dry THF (450 mL) previously cooled to −65° C., was added 1M LiHMDS in THF (115 mL) dropwise. The resulting solution was stirred at −35° C. for 30 minutes. Then the mixture was again cooled to −65° C. and bromoacetonitrile (22 mL) dissolved in dry THF (180 mL) was added. The mixture was left stirring for a further 30 min at the same temperature. The reaction was quenched with saturated ammonium chloride solution (675 mL), THF was evaporated in vacuo and the crude mixture was extracted with EtOAc (2×675 mL). The organic layer was evaporated and the crude material was purified by chromatography on silica gel using cyclohexanes and ethyl acetate (8:2) affording the title compound (51.3 g) as a yellow thick oil.

후처리

  1. temperatureThen the mixture was again cooled to −65° C.
  2. additionwas added
  3. waitThe mixture was left
  4. stirringstirring for a further 30 min at the same temperature
  5. customThe reaction was quenched with saturated ammonium chloride solution (675 mL), THF
  6. customwas evaporated in vacuo
  7. extractionthe crude mixture was extracted with EtOAc (2×675 mL)
  8. customThe organic layer was evaporated
  9. customthe crude material was purified by chromatography on silica gel

출처 및 근거

ORD 기록
ord-ed02b033b2d94ab8bdac653334b4405a
출처 데이터셋
uspto-grants-2010_09
특허 번호
US07803833B2

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