2-Phenyl-3-isopropyl-5-[[4-[2-(cyclopropylmethoxy)ethyl]phenoxy]methyl]oxazolidine → Betaxolol

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Reaction Steps

2.25 g of 2-Phenyl-3-isopropyl-5-[[4-[2-(cyclopropyl methoxy)ethyl]phenoxy]methyl]oxazolidine from Example 4 was dissolved in a mixture of 10 mLs isopropanol, 10 mLs 5% aqueous hydrochloric acid. It was stirred at room temperature for 16 hrs. The isopropanol was removed under reduced pressure and 30 mLs 1% hydrochloric acid was added. The aqueous phase was washed with 15 mLs of toluene then basified and extracted twice with 10 mL portions of toluene. After removal of the solvent under reduced pressure 1.3 g of white solid was obtained (74% crude yield of betaxolol base). Betaxolol base was converted into its hydrochloride salt by dissolution in toluene and treatment with 1 equivalent of hydrochloric acid in isopropanol. Upon removal of isopropanol under reduced pressure and cooling of the toluene solution the hydrochloride salt of betaxolol was obtained. This solid is recrystallized twice from acetone, 4 mL/g, the second time with charcoal treatment to give a white crystalline solid with a melting point of 111.5°-112.5° C.

Provenance & Evidence