Methanol → (4S)-1-[(2H-1,3-Benzodioxol-5-yl)methyl]-4-{(3,3-dimethylbutanoyl)[(3-methoxyphenyl)methyl]amino}-L-proline

HRID 1594244노트

반응식

HRID 1594244 반응식
O.[OH-].[Li+].[O:4]1[C:8]2[CH:9]=[CH:10][C:11]([CH2:13][N:14]3[CH2:18][C@@H:17]([N:19]([C:29](=[O:35])[CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH3:28])[CH:22]=4)[CH2:16][C@H:15]3[C:36]([O:38]C)=[O:37])=[CH:12][C:7]=2[O:6][CH2:5]1.CO>O>[O:4]1[C:8]2[CH:9]=[CH:10][C:11]([CH2:13][N:14]3[CH2:18][C@@H:17]([N:19]([C:29](=[O:35])[CH2:30][C:31]([CH3:34])([CH3:32])[CH3:33])[CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH3:28])[CH:22]=4)[CH2:16][C@H:15]3[C:36]([OH:38])=[O:37])=[CH:12][C:7]=2[O:6][CH2:5]1

참가 물질

5

반응물 3

HCID 887MethanolHCID 168937Lithium hydroxide, monohydrateHCID 20578939HCID 20578939, 화합물

생성물 1

HCID 20578929(4S)-1-[(2H-1,3-Benzodioxol-5-yl)methyl]-4-{(3,3-dimethylbutanoyl)[(3-methoxyphenyl)methyl]amino}-L-proline수율 91.2%

시약·촉매·용매 1

HCID 962Water용매

실험 절차

Lithium hydroxide monohydrate (17 mg, 0.405 mmol) was added to a solution of methyl (2S,4S)-1-(1,3-benzodioxol-5-ylmethyl)-4-[(3,3-dimethylbutanoyl)(3-methoxybenzyl)amino]tetrahydro-1H-2-pyrrolecarboxylate (20) (100 mg, 0.20 mmol) in 66% v/v methanol in water (1.0 mL). The mixture was stirred overnight at room temperature, then the solvent was removed under reduced pressure and the residue partitioned between dichloromethane (1.0 mL) and water (1.0 ml). The aqueous phase was acidified with 1.0 M aqueous citric acid solution and the two layers were vigorously stirred for 10 min at room temperature. The layers were separated and the aqueous layer was back-extracted with dichloromethane. The combined dichloromethane extracts were dried (MgSO4) and evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel using dichloromethane/ethyl acetate (1:1, v/v) and then dichloromethane/methanol (9:1, v/v) as eluents to give the title acid (21) (88 mg, 91%) as an off-white solid:

후처리

  1. customthe solvent was removed under reduced pressure
  2. customthe residue partitioned between dichloromethane (1.0 mL) and water (1.0 ml)
  3. stirringthe two layers were vigorously stirred for 10 min at room temperature
  4. customThe layers were separated
  5. extractionthe aqueous layer was back-extracted with dichloromethane
  6. dry with materialThe combined dichloromethane extracts were dried (MgSO4)
  7. customevaporated under reduced pressure
  8. customThe residue was purified by flash column chromatography on silica gel

출처 및 근거

ORD 기록
ord-f290ff5886f048919fda69d7af83cc53
출처 데이터셋
uspto-grants-2007_11
특허 번호
US07300929B2

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