Sodium triacetoxyborohydride → N-({1-[4-Hydroxy-4-(6-methoxy-pyridin-3-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

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Reaction Steps

4-Hydroxy-4-(6-methoxy-pyridin-3-yl)-cyclohexanone, as prepared in Step B of this example, (300 mg, 1.36 mmol) and N-(azetidin-3-ylcarbamoylmethyl)-3-trifluoromethyl-benzamide HCl salt, as prepared in Step D of this example, (460 mg, 1.36 mmol) in DCM (5 mL) were treated with TEA (1 mL, 7.12 mmol) for 10 min followed by NaBH(OAc)3 (860 mg, 4.07 mmol) for another 4 hours at room temperature. The reaction was quenched with saturated sodium bicarbonate. The organic layer was separated and the aqueous layer was extracted 3 times with chloroform and IPA “cocktail” (˜3:1, v/v). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated to give the crude product, which was then purified by a CombiFlash® system using ethyl acetate and 7N NH3 in MeOH as eluent (from pure ethyl acetate to 5% 7N NH3 in MeOH in ethyl acetate) to afford two title compounds as white solids: a less polar isomer, and a more polar isomer.

Provenance & Evidence