Trifluoroacetic acid → 4-[(R)-4-(3,4-Dichloro-phenyl)-3-methyl-2-oxo-piperazin-1-yl]-butyric acid
Reaction equation
FC(F)(F)C(O)=O.C([O:12][C:13](=[O:37])[CH2:14][CH2:15][CH2:16][N:17]([C:24](=[O:36])[C@H:25]([NH:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([Cl:35])[CH:29]=1)[CH3:26])[CH2:18][CH:19](OC)OC)(C)(C)C.C([SiH](CC)CC)C.C(N(CC)CC)C>ClCCl>[Cl:35][C:30]1[CH:29]=[C:28]([N:27]2[CH2:19][CH2:18][N:17]([CH2:16][CH2:15][CH2:14][C:13]([OH:12])=[O:37])[C:24](=[O:36])[C@H:25]2[CH3:26])[CH:33]=[CH:32][C:31]=1[Cl:34]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
0.69 ml (9.00 mmol) of trifluoroacetic acid was added to a cooled solution (0° C.) of 0.28 g (0.60 mmol) 4-[[(R)-2-(3,4-dichloro-phenylamino)-propionyl]-(2,2-dimethoxy-ethyl)-amino]-butyric acid tert-butyl ester (62% ee) in 6 ml of dichloromethane. After 30 min the ice bath was removed, then after 1 h, 0.49 ml (3.00 mmol) of triethylsilane was added. After 16 h the reaction mixture was cooled to 0° C. and treated with 1.25 ml (9.00 mmol) of triethylamine, then after 15 min partitioned between Et2O (3×)/aqueous 10% KHSO4, the organic phases were washed with aqueous 10% KHSO4 and aqueous 10% NaCl, dried over Na2SO4 and evaporated. The residue was precipitated (dichloromethane/n-pentane) to give 0.198 g (96%) of the titled compound as brown viscous oil. MS: 345.07 (MH+, 2Cl).
Workup
- customAfter 30 min the ice bath was removed
- customafter 15 min partitioned between Et2O (3×)/aqueous 10% KHSO4
- washthe organic phases were washed with aqueous 10% KHSO4 and aqueous 10% NaCl
- dry with materialdried over Na2SO4
- customevaporated
- customThe residue was precipitated (dichloromethane/n-pentane)
Sources & evidence
- ORD record
- ord-b353c46a0db14abc98fa199dc1653f91
- Source dataset
- uspto-grants-2013_05
- Patent number
- US08445674B2
Reaction notes
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