Sodium borohydride → Tert-butyl 4-{[6-(hydroxymethyl)-2-(trifluoromethyl)pyrimidin-4-yl]amino}piperidine-1-carboxylate

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Reaction Steps

Sodium tetrahydroborate (73 mg, 1.9 mmol) was added to a solution of tert-butyl 4-{[6-formyl-2-(trifluoromethyl)pyrimidin-4-yl]amino}piperidine-1-carboxylate (0.90 g, 1.9 mmol, from Step 3) in Isopropyl alcohol (15 mL) at 0° C. After stirring at this temperature for 1.5 hours, the reaction was quenched by the addition of saturated ammonium chloride. The mixture was further diluted with water and extracted with EtOAc. The organic extract was washed with water and brine, dried over sodium sulfate, filtered and concentrated. Flash chromatography on a 40 g silica gel cartridge, eluting with a gradient from 0-100% EtOAc in hexanes afforded product as a white solid (0.58 g, 80% over the two steps). 1H NMR (400 MHz, CDCl3) δ 6.50 (s, 1H), 4.66 (d, J=5.1 Hz, 2H), 4.30-3.89 (m, 2H), 2.95 (t, J=12.0 Hz, 2H), 2.73 (t, J=5.2 Hz, 1H), 2.22-1.88 (m, 2H), 1.53-1.33 (m, 11H). 19F NMR (376 MHz, CDCl3) δ −71.74 (s). LCMS (M+H)+: 377.1.

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