Nitrogen → Tert-butyl {1-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxybut-3-en-2-yl}carbamate

Participants

Reaction Conditions

Reaction Steps

To N-Boc-allylamine (50.0 g, 0.318 mol) in anhydrous THF (800 mL) at −78° C. was added sec-butyllithium (1.30 M in cyclohexane, 538.0 mL, 0.7 mol) dropwise under a stream of N2 gas. The resulting yellow solution was stirred at −78° C. for an additional 2 hours, after which time ZnCl2 (1.1 M in Et2O, 349.8 mL, 0.35 mol) was added. The solution was stirred for 1 hour before 3,5-bis-trifluoromethylbenzaldehyde (169.3 g, 0.700 mol) was added to the clear solution. The mixture was stirred at −78° C. for 1 hour before quenching with acetic acid (227 mL). The reaction was poured into ice water (2 L) and the organic layer was washed with aqueous saturated NaHCO3 (2 L×2) and brine (1 L), was dried (MgSO4), and concentrated. The crude material was recrystallized from petroleum ether (300 mL) to yield tert-butyl {1-[3,5-bis(trifluoromethyl)phenyl]-1-hydroxybut-3-en-2-yl}carbamate (57 g) as a white powder. In total this process yielded 2.8 kg of material. MS ESI calc'd. for C17H20F6NO3 [M+H]+ 400.1, found 400.0.

Provenance & Evidence