Sodium Carbonate → HCID 67127447, compound

Participants

Reaction Conditions

Reaction Steps

(R)-2-(4-Aminobiphenyl-3-yl)-4-cyclopropyl-1,1,1-trifluorobut-3-yn-2-ol methane-sulfonate (CN46630-MSA) of example 2 (14.7 g, 34.4 mmol) in ethyl acetate/heptanes (1:1 v/v, 27.9 g) was charged in a jacketed 150 mL-reactor with agitator and off-gas scrubber with caustic soda. After addition of aqueous Na2CO3 (12%-w/w, 32.3 g, 36.4 mmol, formation of gas during addition!) the mixture was stirred for 15 min at 15° C. The aqueous phase was separated and discarded. Aqueous Na2CO3 (12%-w/w, 41 g, 46 mol) and ethyl acetate (20 g) were charged to the organic phase. Triphosgene (4.41 g, 14.9 mmol) was added in portions over a period of 25 min at 10° C. The reaction mixture was stirred for 2 h at 8° C. The mixture was diluted with ethyl acetate (45 g) and the phases were separated. The aqueous phase was discarded. The organic phase was washed with water (12 mL), dried over MgSO4, filtered and concentrated and dried at 50° C. under reduced pressure to obtain (R)-4-(cyclopropylethynyl)-6-phenyl-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one (CN46685, compound of formula I, wherein R1 is trifluoromethyl, R2 is cyclopropyl, R8 is 6-phenyl, R9 is hydrogen and R10 is hydrogen) (12.1 g, 33.9 mmol, 98%) as a yellowish solid (99.5% purity, according to Method C).

Provenance & Evidence