Pyridine → 2-Morpholin-4-ylethyl (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoate

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Reaction Steps

Following the general procedure for the preparation of carboxylic esters from carboxylic acids of Description 15, (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoic acid (11) (0.73 g, 1.9 mmol) dissolved in 20 mL of anhydrous dichloromethane (DCM) was reacted with 1.1 mL (2.2 mmol) of oxalyl chloride (2.0 M in DCM). After completion of the reaction, a solution of 0.76 g (5.8 mmol) of 2-morpholin-4-yl ethanol and 0.16 mL of pyridine (0.15 g, 1.9 mmol) in 10 mL of anhydrous dichloromethane (DCM) was added to the acid chloride. 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=1:2) as eluent to provide 0.42 g (44% yield) of the title compound (26a) as a colorless oil. Rf=0.31 (EtOAc/Hxn=1.2). 1H NMR (400 MHz, CDCl3): δ=1.09 (s, 3H), 1.11 (s, 3H), 2.25-2.32 (m, 2H), 2.49-2.53 (m, 4H), 2.62-2.65 (m, 2H), 3.22-3.26 (m, 2H), 3.63-3.68 (m, 6H), 3.87 (s, 1H), 4.03 (d, J=9.2 Hz, 1H), 4.22 (d, J=9.6 Hz, 1H), 4.24-4.30 (m, 1H), 4.37 (d, J=11.2 Hz, 1H), 4.37-4.43 (m, 1H), 4.67 (d, J=11.2 Hz, 1H), 7.26-7.36 (m, 5H) ppm. MS (ESI) m/z 492.04 (M+H)+. The analytical data was consistent with the proposed structure.

Provenance & Evidence