Sodium Chloride → 1-Piperidinecarboxylic acid, 3-(2-thiazolylcarbonyl)-, 1,1-dimethylethyl ester, (3S)-

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Reaction Conditions

Reaction Steps

136.6 g (0.32 mol) of n-butyllithium (15% in n-hexane) were added dropwise at −68° C. to a solution of 25 g (0.291 mol) of thiazole in 1 l of tetrahydrofuran. The mixture was warmed to 0° C. and subsequently cooled to −40° C. This mixture was then added dropwise to a solution of 79.2 g (0.291 mol) of tert-butyl (S)-3-(methoxymethylcarbamoyl)piperidine-1-carboxylate in 1.4 l of tetrahydrofuran at −50° C. The reaction mixture was then slowly warmed to 0° C., and 2 l of ice-water were added. After addition of 2 l of water and 2 l of saturated sodium chloride solution, the crude mixture was extracted with a total of 4 l of ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried over sodium sulfate and evaporated. The crude product (87 g) was chromatographed over a silica-gel column, giving 76.4 g of tert-butyl (S)-3-(thiazole-2-carbonyl)piperidine-1-carboxylate as brown resin; rotation value in methanol [α]20D=+27.4°; 1H NMR (500 MHz, DMSO) δ 8.22 (d, J=3.0, 1H), 8.17 (d, J=3.0, 1H), 4.22-3.86 (m, 1H), 3.84-3.69 (m, 2H), 3.60-3.52 (m, 1H), 3.20-3.05 (m, 1H), 2.08-1.92 (m, 2H), 1.89-1.60 (m, 2H), 1.35 (s, 9H).

Provenance & Evidence