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

HRID 1267536ノート

反応式

HRID 1267536 の反応式
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

参加物

5

反応物 3

HCID 887MethanolHCID 168937Lithium hydroxide, monohydrateHCID 20578939HCID 20578939、化合物

生成物 1

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

試薬・触媒・溶媒 1

HCID 962Water溶媒

実験手順

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:

後処理

  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

出典と根拠

ORDレコード
ord-24761cec817145168ff1f7adf1c98d14
出典データセット
uspto-grants-2003_04
特許番号
US06552016B1

反応ノート

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