Trifluoroacetic acid → HCID 86673729, compound

Participants

Reaction Steps

A solution of 3-allyl-5-hydroxy-3-isopropyl-1-(5-(trifluoromethyl)-2-(triisopropylsilyloxy)benzyl)pyrrolidin-2-one (approximately 525 mg, 1.02 mmol) in THF (13 mL) was charged with tris(dimethylamino)sulfonium difluorotrimethylsilicate (366 mg, 1.33 mmol) and the resulting mixture was stirred for 30 min. At this time the mixture was charged with TFA (0.394 mL, 5.11 mmol) and 4 angstrom molecular sieves (500 mg). This solution was stirred for 12 h, at which time it was diluted with EtOAc and washed 2× with brine. The organic layer was dried (MgSO4) and concentrated on a rotary evaporator. The residue was purified using a 12 g silica gel cartridge and 20:1 Hex/EtOAc to 3:1 Hex/EtOAc to elute 2-allyl-2-isopropyl-7-(trifluoromethyl)-2,3,3a,9-tetrahydro-1H-benzo[e]pyrrolo[2,1-b][1,3]oxazin-1-one (177 mg, 0.52 mmol, 51% yield) as a clear oil, 1:1 mixture of diastereomers. LC/MS [M+H]+=340.15, HPLC tR=1.99 min [Waters Sunfire C18 4.6×50 mm column, 3 min gradient from 10/90/0.1 MeOH/H2O/TFA to 90/10/0.1 MeOH/H2O/TFA at 4 mL/min flow rate]. 1H-NMR (400 MHz, CDCl3) δ=7.26 (d, J=8.0 Hz, 1H), 7.21 (s, 1H), 6.80 (d, J=8.0 Hz, 1H), 5.56 (m, 1H), 5.2-4.8 (m, 3H), 4.16 (m, 1H), 2.3-1.8 (m, 5H), 0.8-0.6 (m, 6H).

Provenance & Evidence