4-tert-Butylphenyl glycidyl ether, (+)- → 1'-[(2S)-3-(4-tert-butylphenoxy)-2-hydroxypropyl]spiro[naphtho[1,2-b][1,4]oxathiine-2,4'-piperidine]-5,6-dione

Participants

Reaction Conditions

Reaction Steps

To a mixture of spiro[naphtho[1,2-b][1,4]oxathiine-2,4′-piperidine]-5,6-dione (10.0 g, 33.18 mmol) in absolute ethanol (100 mL) was added (2S)-2-[(4-tert-butylphenoxy)methyl]oxirane (8.9 g, 43.14 mmol). The reaction mixture was stirred at 90° C. for 15 h (sometimes the reaction is complete within 2-3 hours). The reaction mixture was cooled to room temperature the solvent was removed under reduced pressure. The crude product was purified by flash column chromatography (SiO2, 10% EtOAc in dichloromethane to 50% EtOAc in dichloromethane) to give the desired product as a purple solid (8.1 g, 49%). M.p.=155-157° C.; 400 MHz 1H NMR (CDCl3) δ: 8.1-8.03 (m, 1H), 7.8-7.74 (m, 1H), 7.7-7.6 (m, 1H), 7.55-7.45 (m, 1H), 7.35-7.28 (m, 2H), 6.9-6.8 (m, 2H), 4.10-4.17 (m, 1H), 4.0-3.93 (m, 2H), 2.99-2.95 (s, 3H), 2.86-2.74 (m, 2H), 2.7-2.64 (m, 2H), 2.6-2.51 (m, 1H), 2.22-2.13 (m, 2H), 1.98-1.84 (m, 2H), 1.3 (s, 9H); LCMS: 508 [M+H]; enantiomeric excess determined from chiral HPLC: 98%; Chiral HPLC Rt=50.98 min

Provenance & Evidence