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

HRID 1267536Notes

Reaction equation

HRID 1267536 reaction equation
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

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

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:

Workup

  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

Sources & evidence

ORD record
ord-24761cec817145168ff1f7adf1c98d14
Source dataset
uspto-grants-2003_04
Patent number
US06552016B1

Reaction notes

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