Water → (3R)-4-((tert-butoxycarbonyl)amino)-3-((tert-butyldimethylsilyl)oxy)-1-(3-cyano-5-fluorophenyl)butyl methanesulfonate

HRID 513011Notes

Reaction equation

[Si:1]([O:8][C@H:9]([CH2:19][CH:20]([C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[C:24]([C:29]#[N:30])[CH:23]=1)[OH:21])[CH2:10][NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:31][S:32](Cl)(=[O:34])=[O:33].O>C(Cl)Cl>[CH3:31][S:32]([O:21][CH:20]([C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[C:24]([C:29]#[N:30])[CH:23]=1)[CH2:19][C@@H:9]([O:8][Si:1]([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2])[CH2:10][NH:11][C:12]([O:13][C:14]([CH3:16])([CH3:17])[CH3:15])=[O:18])(=[O:34])=[O:33]

Participants

Conditions

Temperature: -60 °C

Procedure

To a solution of tert-butyl ((2R)-2-((tert-butyldimethylsilyl)oxy)-4-(3-cyano-5-fluorophenyl)-4-hydroxybutyl)carbamate (I-10) (5.3 g, 12.1 mmol) in DCM (50 mL) at −60° C. was added TEA (5.1 mL, 36.3 mmol) and MsCl (0.98 mL, 12.2 mmol). The resulting mixture was stirred at −60° C. for 2 hours. The reaction was poured into water, diluted with DCM and washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography on silica gel with EtOAc/hexanes gradient as eluant to yield (3R)-4-((tert-butoxycarbonyl)amino)-3-((tert-butyldimethylsilyl)oxy)-1-(3-cyano-5-fluorophenyl)butyl methanesulfonate (I-11). MS m/z 539.1 (M+23)+. Compound decomposed on standing. Used immediately in next reaction without delay.

Workup

washwashed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by column chromatography on silica gel with EtOAc/hexanes gradient as eluant

Sources & evidence

ORD record: ord-fdd9db880e944a9aab7202f4f9e51d5d
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09102671B2

Reaction notes

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