Imidazole → (S)-2-benzyloxycarbonylamino-4-(t-butyl-dimethyl-silanyloxy)-butyric acid methyl ester

HRID 19329Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:19])[C@@H:4]([NH:8][C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])[CH2:5][CH2:6][OH:7].N1C=CN=C1.[C:25]([Si:29](Cl)([CH3:31])[CH3:30])([CH3:28])([CH3:27])[CH3:26].CN(C)C=O>O1CCCC1.O>[CH3:1][O:2][C:3](=[O:19])[C@@H:4]([NH:8][C:9]([O:11][CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:10])[CH2:5][CH2:6][O:7][Si:29]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:31])[CH3:30]

Participants

Conditions

Temperature: 25 °C

Procedure

In a flask under argon was placed (S)-2-benzyloxycarbonylamino-4-hydroxy-butyric acid methyl ester (535 mg, 2.0 mmol) in tetrahydrofuran (5 mL). To this mixture was then added imidazole (330 mg, 4.8 mmol) and t-butyl dimethyl silyl chloride (360 mg, 2.4 mmol) and within a minute solids started to appear and N,N-dimethylformamide (1 mL) was added to solubilize the material. The mixture was stirred for 16 h at 25° C. and then diluted with water (50 mL) and the aqueous layer extracted with diethyl ether (2×50 mL) dried over sodium sulfate, filtered and concentrated in vacuo with silica gel (2 g). Purification by Biotage flash chromatography (Aspire 40 g column, 16% ethyl acetate/hexanes) afforded (S)-2-benzyloxycarbonylamino-4-(t-butyl-dimethyl-silanyloxy)-butyric acid methyl ester (478 mg, 63%) as a colorless oil.

Workup

customIn a flask under argon was placed
extractionthe aqueous layer extracted with diethyl ether (2×50 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo with silica gel (2 g)
customPurification by Biotage flash chromatography (Aspire 40 g column, 16% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-bfadb3072a174cfa816610de01c586b0
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07741327B2

Reaction notes

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