Hydrochloric Acid → HCID 69590731, compound

Participants

Reaction Steps

The racemic ester of Example 4 (200 g; 1.11 mol) was added to a stirred solution of acetone (0.80 L) and potassium phosphate buffer (pH=7.2; 1.2 L). The hazy solution was stirred at 20–25° C. and Novozyme 435 (50 g), immobilized Candida Antarctica lipase B, was added to the reaction mixture. The suspension was then stirred at 20–25° C. for 120 hours. During this time a 1M aqueous solution of sodium hydroxide was added so as to maintain a pH of 8.1. Concentrated hydrochloric acid (45 ml) was added to pH 2–3 and the heterogeneous reaction mixture was filtered. The filter cake was washed with n-heptane (1.0 L). The two phase filtrate was separated and the aqueous phase re-extracted with tert-butylmethyl ether (0.50 L). The combined organic phases were extracted with a 1M aqueous solution of sodium hydroxide (0.4 L). The aqueous solution was then adjusted to pH 1–2 by the addtion of concentrated hydrochloric acid (40 ml) and extracted twice with tert-butylmethyl ether (0.40 L, then 0.20 L). The combined organic phases were washed with demineralised water (0.40 L) and concentrated in vacuo to give the title compound (56.5 g) in 33.5% yield as a pale yellow oil which crystallised on standing.

Provenance & Evidence