Imidazole → 5(S)-tert-butoxycarbonylamino-4(S)-tert-butyldimethylsilyloxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxy-propyloxy)-phenyl]-octanoic acid

HRID 744827Notes

Reaction equation

HRID 744827 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:18][C@@H:19]([CH:35]([CH3:37])[CH3:36])[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[C:23]([O:29][CH2:30][CH2:31][CH2:32][O:33][CH3:34])[CH:22]=1)[C@@H:10]([OH:17])[CH2:11][C@@H:12]([CH3:16])[C:13]([OH:15])=[O:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Si:38](Cl)([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39].N1C=CN=C1>CN(C)C=O>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:18][C@@H:19]([CH:35]([CH3:37])[CH3:36])[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[C:23]([O:29][CH2:30][CH2:31][CH2:32][O:33][CH3:34])[CH:22]=1)[C@@H:10]([O:17][Si:38]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39])[CH2:11][C@@H:12]([CH3:16])[C:13]([OH:15])=[O:14])=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 228658195(S)-Tert-butoxycarbonylamino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid

Product 1

HCID 228658215(S)-tert-butoxycarbonylamino-4(S)-tert-butyldimethylsilyloxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxy-propyloxy)-phenyl]-octanoic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4.45 g of 5(S)-tert-butoxycarbonylamino-4(S)-hydroxy-7(S)-isopropyl-2(R)-methyl-8-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-octanoic acid (crude) are stirred in 45 ml of dimethylformamide with 2.36 g of tert-butyldimethylsilyl chloride and 2.03 g of imidazole for 6 days at room temperature. The mixture is concentrated by evaporation and the residue is partitioned between 10% citric acid solution and ethyl acetate. The organic phase is concentrated and stirred in 20 ml of tetrahydrofuran, 8 ml of water and 20 ml of acetic acid at room temperature for 16 hours. After concentration by evaporation, ice/water is added to the residue and the mixture is then extracted with ethyl acetate. The title compound is obtained from the organic phase after FC (260 g of silica gel, ethyl acetate/hexane=1:1): Rf (ethyl acetate/hexane=1:1)=0.32.

Workup

  1. concentrationThe mixture is concentrated by evaporation
  2. customthe residue is partitioned between 10% citric acid solution and ethyl acetate
  3. concentrationThe organic phase is concentrated
  4. concentrationAfter concentration
  5. customby evaporation, ice/water
  6. additionis added to the residue
  7. extractionthe mixture is then extracted with ethyl acetate

Sources & evidence

ORD record
ord-df72225e4c8e42a69c8973c5ad1f9520
Source dataset
uspto-grants-1996_09
Patent number
US05559111

Reaction notes

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