Pyridine → (1S)-1,3-Dimethyl-2-oxobutyl (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(1,1,2,2-tetramethyl-1-silapropoxy)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-(1,1,2,2-tetramethyl-1-silapropoxy)butanoic acid (15) (2.0 g, 5.0 mmol) dissolved in 25 mL of anhydrous dichloromethane (DCM) was reacted with 0.90 mL (1.31 g, 10 mmol) of oxalyl chloride. Upon completion of the reaction, a solution of 2 mL (1.2 g, 10.0 mmol) of (2S)-2-hydroxy-4-methylpentan-3-one (synthesized following procedures according to Gallop et al., U.S. Pat. No. 6,927,036) and 0.85 mL of pyridine (0.79 g, 10.0 mmol) in 20 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=1:9) as eluent to provide 0.9 g (36% yield) of the title compound (30a) as a colorless oil. Rf=0.39 (EtOAc/Hxn=1:4). 1H NMR (400 MHz, CDCl3): δ=0.05 (s, 3H), 0.10 (s, 3H), 0.94 (s, 9H), 1.09 (s, 6H), 1.12 (d, J=7.2 Hz, 3H), 1.19 (d, J=7.2 Hz, 3H), 1.46 (d, J=7.2 Hz, 3H), 2.32-2.39 (m, 2H), 2.83 (sept., J=7.2 Hz, 1H), 3.31-3.35 (m, 2H), 3.69-3.72 (m, 2H), 4.10-4.13 (m, 3H), 5.24 (q, J=7.2 Hz, 1H) ppm. MS (ESI) m/z 501.09 (M+H)+, 523.03 (M+Na)+. The analytical data was consistent with the proposed structure.

Provenance & Evidence