Trifluoroacetic acid → (S)-4-[(S)-4-(3-Chloro-4-trifluoromethyl-phenyl)-3-methyl-2-oxo-piperazin-1-yl]-3-hydroxy-butyric acid methyl ester

HRID 2095526Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:31])[CH2:4][C@H:5]([OH:30])[CH2:6][N:7]([C:14](=[O:29])[C@@H:15]([NH:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[C:20]([Cl:28])[CH:19]=1)[CH3:16])[CH2:8][CH:9](OC)OC.FC(F)(F)C(O)=O.C([SiH](CC)CC)C.C(N(CC)CC)C.OS([O-])(=O)=O.[K+].CCOC(C)=O>ClCCl>[CH3:1][O:2][C:3](=[O:31])[CH2:4][C@H:5]([OH:30])[CH2:6][N:7]1[CH2:8][CH2:9][N:17]([C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:26])([F:25])[F:27])=[C:20]([Cl:28])[CH:19]=2)[C@@H:15]([CH3:16])[C:14]1=[O:29]

Participants

Conditions

Temperature: 0 °C

Procedure

1.82 g (3.9 mmol) of (S)-4-[[(S)-2-(3-chloro-4-trifluoromethyl-phenylamino)-propionyl]-(2,2-dimethoxy-ethyl)-amino]-3-hydroxy-butyric acid methyl ester were dissolved at RT in 39.0 ml of dichloromethane, cooled (0° C.) and treated with 4.4 ml of trifluoroacetic acid. After 30 min at 0° C. and 2.5 h at RT 3.2 ml (19.3 mmol) of triethylsilane were added and stirred over night at RT. The reaction was neutralized with 8.1 ml (58 mmol) of triethylamine at 0° C. and after 10 min poured on aqueous 10% KHSO4/EtOAc (3×). The organic phases were washed with aqueous 10% KHSO4, saturated NaHCO3, 10% NaCl and dried over Na2SO4 to yield after flash chromatography (SiO2, EtOAc/Heptan from 1:1 to 4:1) 0.114 g (7%) of the titled compound as yellow oil. MS: 409.2 (MH+).

Workup

washThe organic phases were washed with aqueous 10% KHSO4, saturated NaHCO3, 10% NaCl
dry with materialdried over Na2SO4

Sources & evidence

ORD record: ord-e892c271188c4cd68072d1a9b4108973
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08445674B2

Reaction notes

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