Naphthalene → (S)-[2-amino-3-(1-fluoro-cyclohexyl)-propyl]-methyl-carbamic acid tert-butyl ester

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Reaction Steps

A solution of sodium naphalenide in anhydrous DME was prepared by adding anhydrous DME (20 mL) to a mixture of sodium (0.3 g, 13 mmol) and naphthalene (2.1 g, 16 mmol) and stirring the resulting mixture at rt for 2 h. A solution of tert-butyl 3-(1-fluorocyclohexyl)-2-(4-methylphenylsulfonamido)propyl(methyl)carbamate (200 mg, 0.43 mmol) in anhydrous DME (15 mL) was cooled in dry ice-isopropyl alcohol bath. The sodium naphthalenide solution was added dropwise to the well-stirred tosylamide solution until a light green color persisted. The reaction was quenched with water, diluted with EtOAc and washed with 1 N aq HCl. The aqueous phase was basified with K2CO3, and extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo to give (S)-[2-amino-3-(1-fluoro-cyclohexyl)-propyl]-methyl-carbamic acid tert-butyl ester (50 mg, 45%).

Provenance & Evidence