Trifluoroacetic anhydride → HCID 11201679, compound

Participants

Reaction Conditions

Reaction Steps

To a chilled (0° C.) solution of 500 mg (1.1 mmol) of 3-amino-5-methyl-4-[5,5,5-trifluoro-4-(6-fluoro-4-methylchroman-4-ylmethyl)-4-hydroxypent-1-ynyl]benzonitrile in 20 mL of dichloromethane was added 460 μL (3.3 mmol) of trifluoroacetic anhydride. After 15 minutes, the reaction was concentrated in vacuo and the residue three times diluted with ether and concentrated. The resulting oil was dissolved in 1.5 mL of DMSO, and then 0.4 mL (3.2 mmol) of tetramethylguanidine was added and the mixture was warmed at 140° C. in a microwave oven. After 10 minutes, the mixture was cooled and poured onto crushed ice. The resulting solid was collected by filtration, air dried, and chromatographed on silica gel eluting with ethyl acetate-hexanes (gradient: 0-30% EtOAc) to afford two diastereomers. Further purification of the separated diastereomers by preparatory TLC (silica gel, ethyl acetate-hexanes (7:3)) gave first 82 mg (17%) of the title compound as a single diastereomer (M−1=445) and second 80 mg (17%) of the title compound as the opposite diastereomer (M−1=445).

Provenance & Evidence