1-chloroethyl cyclohexanecarboxylate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the general procedure for the preparation of acyloxyalkyl/alkoxycarbonyloxyalkyl carboxylic esters from carboxylic acids of Description 22, (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoic acid (11) (1.2 g, 3.3 mmol) dissolved in 10 mL of anhydrous toluene was reacted with 1.9 g (10.0 mmol) of chloroethyl cyclohexanecarboxylate (24) in the presence of 1.4 g (5.0 mmol) of silver carbonate (Ag2CO3). After work-up, the crude material was purified by silica gel column chromatography using a mixture of ethyl acetate (EtOAc) and hexane (Hxn) (EtOAc/Hxn=1:9→EtOAc/Hxn=1:5) as eluent to provide 0.69 g (39% yield) of the title compound (44a) as a colorless oil. Rf=0.11 (EtOAc/Hxn=1:9). 1H NMR (400 MHz, CDCl3, both diastereomers): δ=1.06-1.08 (m, 6H), 1.23-1.36 (br. m, 3H), 1.44-1.50 (br. m, 2H), 1.53 (d, J=5.6 Hz, 3H), 1.58-1.68 (br. m, 1H), 1.74-1.80 (br. m, 2H), 1.86-1.97 (br. m, 2H), 2.25-2.39 (m, 3H), 3.21-3.26 (m, 2H), 3.63-3.66 (m, 2H), 3.82-3.84 (2s, 1H), 3.96 (d, J=9.2 Hz, 1H), 4.20-4.24 (m, 1H), 4.33-4.37 (2d, J=11.6, 11.6 Hz, 1H), 4.59-4.66 (2d, J=10.8, 11.2 Hz, 1H), 6.91-6.95 (m, 1H), 7.30-7.37 (m, 5H) ppm. MS (ESI) m/z 554.92 (M+Na)+. The analytical data was consistent with the proposed structure. After work-up, the crude material was purified by silica gel column chromatography a mixture of ethyl acetate (EtOAc) and hexane (Hxn) (EtOAc/Hxn=1:9→EtOAc/Hxn=1:5) as eluent