Potassium Carbonate → (4aS,5S,7aS)-7a-(2-fluorophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine

Participants

Reaction Conditions

Reaction Steps

To a solution of N-((4aS,5S,7aS)-7a-(2-fluorophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide (250.2 g, 589.5 mmol) in methanol (1.25 L) was added K2CO3 (81.5 g, 590.0 mmol). The suspension was heated to 65° C. for 6 h. Upon cooling to ambient temperature, the solvent was evaporated under vacuum. To the resulting residue, was added 1.0 N aq NaOH (1.18 L) and THF (502 mL). The heterogeneous mixture was heated to 45° C. for 1 h. The mixture was cooled to ambient temperature, and EtOAc (1.38 L) was added. The aqueous layer was extracted with EtOAc (0.75 L). The organics were combined, washed with saturated aq. NaHCO3 (500 mL) and saturated aq. NaCl (500 mL). The organics were concentrated under vacuum to afford the title compound as a brown oil (184.1 g, 91.6% yield accounting for residual solvents). 1H NMR (500 MHz, DMSO) δ ppm 7.49-7.42 (m, 1H), 7.40-7.33 (m, 1H), 7.26-7.15 (m, 2H), 6.26 (s, 2H), 4.77-4.54 (m, 1H), 4.40 (d, J=8.0 Hz, 1H). 3.80 (dd, J=7.9, 2.3 Hz, 1H), 3.24-3.17 (m, 1H), 3.00 (dd, J=13.9, 3.2 Hz, 1H), 2.85 (dd, J=13.9, 3.9 Hz, 1H); 13C NMR (125 MHz, DMSO) δ ppm 159.75 (d, JCF=245.1 Hz), 149.51, 131.31 (d, JCF=3.9 Hz), 130.13 (d, JCF=8.8 Hz), 128.08 (d, JCF=10.4 Hz), 128.28 (q, JCF=282.1 Hz). 124.87 (d, JCF=3.0 Hz), 116.80 (d, J=23.8 Hz). 78.77, 76.80 (q, JCF=30.8 Hz), 66.31, 36.37, 23.27.

Provenance & Evidence