Ammonium Chloride → methyl (E)-6-amino-5-(4-(phenylmethoxy)but-1-enyl)-4-(4-fluorophenyl)-2-(1-methylethyl)nicotinate

Participants

Reaction Conditions

Reaction Steps

To a suspension of (3-benzyloxypropyl)triphenyl-phosphonium bromide (8.55 g, 17.4 mmol) in tetrahydrofuran (15 mL) was added dropwise sodium bis(trimethylsilyl)amide (34.8 mL, 1.0 M in tetrahydrofuran) under nitrogen at −78° C. The reaction was stirred at −78° C. for 30 min, allowed to warm to room temperature and stirred for another 30 min. The mixture was then cooled to −78° C. and a solution of methyl 6-amino-4-(4-fluorophenyl)-5-formyl-2-(1-methylethyl)-3-pyridinecarboxylate (5.0 g, 15.8 mmol) in tetrahydrofuran (10 mL) was added dropwise over 45 min. The resulting mixture was stirred at −78° C. for 30 min, allowed to warm to room temperature and stirred for 2 h. The resulting mixture was then poured into a mixture of ice, ethyl acetate, saturated aqueous NH4Cl and was extracted with ethyl acetate. The combined organic layers were washed with brine and evaporated. The residue was equally divided and portion was purified by a silica gel chromatography (120 g column), using 0% to 45% of ethyl acetate in hexanes. The collected fractions were concentrated to provide methyl (E)-6-amino-5-(4-(phenylmethoxy)but-1-enyl)-4-(4-fluorophenyl)-2-(1-methylethyl)nicotinate as a light orange oil (5.79 g, 82%): LCMS (ESI, pos. ion spectrum) m/z 449 (M+H); HPLC (method 3) tR=3.2 min.

Provenance & Evidence