Potassium trimethylsilanolate → 2-(3-Cyclohexyl-1,1,1-trifluoro-3-(pyrazine-2-carboxamido)propan-2-ylamino)-3,3-dimethylbutanoic acid

HRID 424970Notes

Reaction equation

[CH:1]1([CH:7]([NH:23][C:24]([C:26]2[CH:31]=[N:30][CH:29]=[CH:28][N:27]=2)=[O:25])[CH:8]([NH:13][CH:14]([C:19]([CH3:22])([CH3:21])[CH3:20])[C:15]([O:17]C)=[O:16])[C:9]([F:12])([F:11])[F:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C[Si](C)(C)[O-].[K+]>O1CCCC1.C(OCC)(=O)C>[CH:1]1([CH:7]([NH:23][C:24]([C:26]2[CH:31]=[N:30][CH:29]=[CH:28][N:27]=2)=[O:25])[CH:8]([NH:13][CH:14]([C:19]([CH3:22])([CH3:21])[CH3:20])[C:15]([OH:17])=[O:16])[C:9]([F:11])([F:12])[F:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

Conditions

Temperature: 140 °C

Procedure

The stereoisomer of methyl 2-(3-cyclohexyl-1,1,1-trifluoro-3-(pyrazine-2-carboxamido)propan-2-ylamino)-3,3-dimethylbutanoate designated as 7A1-isomer A (107 mgm), and potassium trimethylsilanolate (124 mgm, 4 eq) in tetrahydrofuran (2.5 mL) were heated to 140° C. in a microwave apparatus for 10 minutes. The reaction mixture was diluted with ethyl acetate, and washed successively with 1N hydrochloric acid, water, brine, and then dried over anhydrous sodium sulfate. Evaporation to dryness under reduced pressure gave crude 2-(3-cyclohexyl-1,1,1-trifluoro-3-(pyrazine-2-carboxamido)propan-2-ylamino)-3,3-dimethylbutanoic acid (8), designated as 8A1-isomer A.

Workup

washwashed successively with 1N hydrochloric acid, water, brine
dry with materialdried over anhydrous sodium sulfate
customEvaporation to dryness under reduced pressure

Sources & evidence

ORD record: ord-3353f46708dd445ab4e541fe5d767b74
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08106059B2

Reaction notes

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