Lithium hydroxide, monohydrate → Lithium 1-methylsulfonylcyclobutanecarboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 1-methylsulfonylcyclobutanecarboxlate (0.10 g, 0.52 mmol) in 2 mL of dioxane and 2 mL of water was added lithium hydroxide monohydrate (44 mg, 1.0 mmol). After stirring at 100° C. for 1 h, the reaction mixture was concentrated to dryness, and the residue was azeotroped with toluene to give the crude lithium 1-methylsulfonylcyclobutanecarboxylate, which was used without further purification. Thus, the crude lithium salt was suspended in 2 mL of anhydrous dimethylformamide, and was added N-(2S,3S)-[3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-amine hydrochloride (0.15 g, 0.52 mmol), tris(pyrrolindinyl)phosphonium hexafluorophosphate (0.41 g, 0.78 mmol) and N-methylmorpholine (0.23 mL, 2.1 mmol). After stirring at room temperature overnight, the reaction mixture was partitioned between water (20 mL) and ether (20 mL). The organic layer was separated, and the aqueous layer was extracted with ether (20 mL). The combined extracts were dried over anhydrous magnesium sulfate, filtered and concentrated to dryness, and the residue was purified by flash chromatography on silica gel eluting with 20 to 40% ethyl acetate in hexane to give the title compound. 1H NMR (500 MHz, CD3OD): δ 7.57 (m, 1H), 7.49 (s, 1H), 7.43 (m, 2H), 7.10 (d, 2H), 6.92 (d, 2H), 4.38 (m, 1H), 3.35-2.63 (m, 7H), 2.93 (s, 3H), 2.14 (m, 1H), 1.98 (m, 1H), 0.98 (d, 3H). LC-MS: m/e 445 (M+H)+ (3.5 min).

Provenance & Evidence