Diisopropylamine → 2,2-Bis(3-(trifluoromethoxy)phenyl)acetonitrile

Participants

Reaction Steps

2,2-Bis(3-(trifluoromethoxy)phenyl)acetonitrile (100 mg, 0.3 mmol) was prepared as described in Example 10 (Procedure13 and 14). To a solution of diisopropyl amine (0.146 mL, 1.04 mmol) in THF (3 mL) at −78° C. was added dropwise n-BuLi (1.6 M in hexane, 0.675 mL, 1.08 mmol) and the reaction mixture was stirred for 5 min. A solution of (2,2-bis(3-(trifluoromethoxy)phenyl)acetonitrile (300 mg, 0.83 mmol) in THF (0.5 mL) was added dropwise to the reaction mixture and stirred for 1 h. tert-Butyl 2-bromoacetate (0.159 mL, 1.08 mmol) was added dropwise, then the cooling bath was removed and the reaction mixture was stirred at rt for 45 min. The reaction mixture was poured into H2O (15 mL) and extracted with diethyl ether (2×15 mL). The combined organic portions were dried over Na2SO4, filtered and concentrated under reduced pressure to yield crude tert-butyl 3-cyano-3,3-bis(3-(trifluoromethoxy)phenyl)propanoate. The crude tert-butyl 3-cyano-3,3-bis(3-(trifluoromethoxy)phenyl)propanoate was purified by a silica gel ISCO cartridge (12 g) with elution at 25 mL/min gradient 0 to 25% EtOAc in hexane to yield a white solid (84 mg, 63% yield). LCMS: RT=2.18 min [M+H] 476.02 (2 min Phenomenex Luna C18 column, 4.6×30 mm eluting with 75-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); NMR: 400 MHz 1H (CDCl3) ppm 1.30 (s, 9 H), 3.33 (s, 2 H), 7.21-7.24 (m, 4 H), 7.36 (d, J=8.35 Hz, 2 H), 7.45 (t, J=8.35 Hz, 2 H).

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