1-Piperazinecarboxylic acid, 4-(ethenylsulfonyl)-, phenylmethyl ester synthesis

Yield:1246203-64-4 43%

Reaction Conditions:

with N-ethyl-N,N-diisopropylamine in dichloromethane at -15 - 0; for 0.75 h;

Steps:

83

A mixture of 11 g (50 mmol) of benzyl 1-piperazinecarboxylate and 16.1 g (125 mmol) of DIPEA in 200 mL CH₂Cl₂ was cooled to -15° C. and 6.3 mL (9.8 g, 60 mmol) of 2-chloroethanesulfonyl chloride was added slowly over 15 min. The mixture was allowed to warm to 0° C. over 30 min and water was then added. The organic layer was separated and washed successively with dil. HCl and aq. NaHCO₃. After drying, the solvent was removed and the residue was chromatographed on silica, eluting with CH₂Cl₂/EtOAc 95:5, to give an oil, which was recrystallized from CH₂Cl₂/hexanes to give 6.64 g (43% yield) of benzyl 4-(vinylsulfonyl)-1-piperazinecarboxylate: mp (CH₂Cl₂/hexanes) 85-87° C.; ¹H NMR (CDCl₃) δ 7.39-7.30 (m, 5H), 6.40 (dd, J=16.6, 9.8 Hz, 1H), 6.25 (d, J=16.6 Hz, 1H), 6.06 (d, J=9.8 Hz, 1H), 5.14 (s, 2H), 3.61 (m, 4H), 3.14 (m, 4H); Anal. Calcd. for C₁₄H₁₈N₂O₄S: C, 54.2; H, 5.85; N, 9.0; Found: C, 54.1; H, 5.7; N, 9.1%.

References:

US2010/249099,2010,A1 Location in patent:Page/Page column 87