Tetrahydrofuran toluene → 1-[6-(Trifluoromethyl)pyridin-3-yl]ethan-1-one

HRID 241847Notes

Reaction equation

CON(C)[C:4](=[O:15])[C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[N:7][CH:6]=1.[CH3:17][Mg]Br.C1(C)C=CC=CC=1.C1COCC1>O1CCCC1>[F:12][C:11]([F:14])([F:13])[C:8]1[N:7]=[CH:6][C:5]([C:4](=[O:15])[CH3:17])=[CH:10][CH:9]=1

Participants

Conditions

Temperature: 0 °C

Procedure

N-Methoxy-N-methyl-6-(trifluoromethyl)nicotinamide (19.1 g, 81.6 mmol) was dissolved in tetrahydrofuran (410 mL). The system was purged with N2 and then cooled to 0° C. 1.4 M of methylmagnesium bromide in toluene/THF (75:25) (87.4 mL, 122.4 mmol) was added dropwise using an additional funnel. At the end of the addition the mixture was cloudy off-white. The mixture was stirred at 0° C. for 1 hour and carefully quenched by dropwise addition of 1 M aq. HCl (150 mL) and diluted with ethyl ether (300 mL) and EtOAc (100 mL). The organic layer was separated and washed with 0.1 M aq. NaOH (200 mL) and brine (2×50 mL), dried (Na2SO4), and concentrated to yield a light yellow solid (15.04 g, 98%).

Workup

customThe system was purged with N2
additionAt the end of the addition the mixture
customcarefully quenched by dropwise addition of 1 M aq. HCl (150 mL)
additiondiluted with ethyl ether (300 mL) and EtOAc (100 mL)
customThe organic layer was separated
washwashed with 0.1 M aq. NaOH (200 mL) and brine (2×50 mL)
dry with materialdried (Na2SO4)
concentrationconcentrated

Sources & evidence

ORD record: ord-db5a7a8bd7cc4c14a82c645f8a688e38
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653091B2

Reaction notes

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