Sodium Hydroxide → HCID 71522264, compound

Participants

Reaction Steps

The mixture of Example 222A (285 mg, 0.868 mmol), methanol (5 mL), sodium acetate (85 mg, 1.042 mmol) and hydroxylamine hydrochloride (72.4 mg, 1.042 mmol) was heated in a 50° C. oil bath. After 15 minutes, the reaction mixture was cooled to room temperature and added ammonium acetate (736 mg, 9.55 mmol), sodium cyanoborohydride (164 mg, 2.60 mmol), and titanium(III)chloride (2.414 mL, 1.910 mmol) (dropwise to keep the internal temperature at about 35° C.). After 10 minutes, 2N NaOH was added and the mixture was extracted with EtOAc. The organic phase was dried (Na2SO4), filtered, and concentrated. Purification of the residue using a Waters C8 OBD SunFire 30 mm×75 mm eluted with acetonitrile/0.1% TFA afforded Example 222B as a trifluoroacetate salt in 34% yield. MS (ESI+) M/Z 330 (M+H). 1H NMR (500 MHz, CD3OD) δ ppm 7.47-7.49 (m, 2H), 7.21-7.23 (m, 2H), 3.87 (d, J=9.5 Hz, 1H), 3.35 (q, J=8.4 Hz, 1H), 2.51-2.58 (m, 1H), 2.39-2.47 (m, 1H), 2.32-2.39 (m, 1H), 2.24-2.32 (m, 1H), 1.90-2.05 (m, 2H), 1.76-1.85 (m, 1H), 1.57-1.76 (m, 3H), 1.25-1.45 (m, 3H).

Provenance & Evidence