Acetonitrile → 3-(2-Chloro-4-methoxy-phenyl)-1,1,1-trifluoro-2-(5-methyl-pyrazin-2-yl)-butan-2-ol

HRID 1095864Notes

Reaction equation

HRID 1095864 reaction equation
[F:1][C:2]([Si](C)(C)C)([F:4])[F:3].[Cl:9][C:10]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:11]=1[CH:18]([CH3:28])[C:19]([C:21]1[CH:26]=[N:25][C:24]([CH3:27])=[CH:23][N:22]=1)=[O:20].O.O.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.CC#N>C1COCC1.C(O)(C(F)(F)F)=O>[Cl:9][C:10]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:11]=1[CH:18]([CH3:28])[C:19]([C:21]1[CH:26]=[N:25][C:24]([CH3:27])=[CH:23][N:22]=1)([OH:20])[C:2]([F:4])([F:3])[F:1]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 552549(Trifluoromethyl)trimethylsilaneHCID 11726816Tetrabutylammonium Fluoride TrihydrateHCID 666991162-(2-Chloro-4-methoxy-phenyl)-1-(5-methyl-pyrazin-2-yl)-propan-1-one

Product 1

HCID 252527573-(2-Chloro-4-methoxy-phenyl)-1,1,1-trifluoro-2-(5-methyl-pyrazin-2-yl)-butan-2-olYield 24.1%

Reagents, catalysts & solvents 2

HCID 6422Trifluoroacetic acidSolventHCID 8028TetrahydrofuranSolvent

Procedure

Trifluoromethyltrimethylsilane (2N in THF, 0.6 mL, 1.2 mmol) was added at 0° C. to a solution of 2-(2-chloro-4-methoxy-phenyl)-1-(5-methyl-pyrazin-2-yl)-propan-1-one (290 mg, 1.0 mmol) in THF (7 mL), followed by the addition of tetrabutylammonium fluoride trihydrate (31 mg, 0.1 mmol). After stirring overnight at r.t., the title compound (87 mg, 24%) was isolated from the reaction mixture by reversed-phase, preparative HPLC (Agilent Zorbax XdB-C18 column, solvent gradient 5-95% CH3CN in 0.1% TFA[aq]). 1H NMR (300 MHz, CDCl3) δ 8.75 (1H, s), 8.13 (1H, s), 7.44 (1H, d), 6.64 (1H, d), 6.59 (1H, dd), 5.90 (1H, s), 4.33 (1H, q), 3.67 (3H, s), 2.50 (3H, s), 1.54 (3H, d); MS (m/e, ISP neg. ion)=359.1 [M−H+].

Sources & evidence

ORD record
ord-3827c50d0e91488badee88dfa72b6d00
Source dataset
uspto-grants-2012_03
Patent number
US08138189B2

Reaction notes

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