Tetrabutylammonium Fluoride → 3,3,3-trifluoro-N-(2-(hydroxymethyl)-4-methoxyphenyl)propanamide

HRID 1472712Notes

Reaction equation

[Si]([O:8][CH2:9][C:10]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:11]=1[NH:18][C:19](=[O:25])[CH2:20][C:21]([F:24])([F:23])[F:22])(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[F:22][C:21]([F:23])([F:24])[CH2:20][C:19]([NH:18][C:11]1[CH:12]=[CH:13][C:14]([O:16][CH3:17])=[CH:15][C:10]=1[CH2:9][OH:8])=[O:25]

Participants

Conditions

Temperature: 35 °C

Procedure

To a solution of N-(2-((tert-butyldimethylsilyloxy)methyl)-4-methoxyphenyl)-3,3,3-trifluoropropanamide (20.0 g) in anhydrous THF (200 mL) was added a solution of TBAF (16.6 g, 63.6 mmol) in anhydrous THF (60 mL). The mixture was stirred at 35° C. for 30 minutes. The mixture was quenched with ice-water. An aqueous/EtOAc workup was followed by removal of volatiles in vacuo. The crude product was purified by column chromatography on silica gel (PE/EtOAc=1/2) to give the product. 1H NMR (CDCl3 400 MHz): δ 8.60 (brs, 1H), 7.82 (d, J=8.8 Hz, 1H), 6.85 (dd, J=9.2, 3.2 Hz, 1H), 6.75 (d, J=2.8 Hz, 1H), 4.65 (s, 2H), 3.80 (s, 3H), 3.23 (q, J=10.4 Hz, 2H).

Workup

customThe mixture was quenched with ice-water
customAn aqueous/EtOAc workup was followed by removal of volatiles in vacuo
customThe crude product was purified by column chromatography on silica gel (PE/EtOAc=1/2)
customto give the product

Sources & evidence

ORD record: ord-6ddabf29aedd44a9b5e6ad9c0d33b5b3
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09012646B2

Reaction notes

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