Patent ID: 8115002

Claim:
A process for the preparation of a ketal (1000), the process comprising converting a hexahydroisoquinoline (800) to a ketal (1000) in a series of steps, the series of steps comprising (a) converting hexahydroisoquinoline (800) to a N-formyl derivative (900) with a formylating agent and (b) converting the N-formyl derivative (900) to the ketal (1000) with a ketalizing agent in the presence of an acid catalyst, whereby the conversion of the hexahydroisoquinoline (800) to the ketal (1000) proceeds without an intermediate crystallization of the N-formyl derivative (900); wherein the conversion of the hexahydroisoquinoline (800) to the N-formyl derivative (900) produces a formylation product mixture containing the N-formyl derivative (900) and unreacted formylating agent, the unreacted formylating agent being separated from the N-formyl derivative (900) by including in the formylation product mixture a liquid composition having a boiling point that is greater than the boiling point of the formylating agent, and the formylation product mixture being heated to remove unreacted formylating agent and leave the N-formyl derivative (900) dissolved in the liquid composition; and, wherein the hexahydroisoquinoline (800), the N-formyl derivative (900), and the ketal (1000) correspond to Formulae (800), (900), and (1000), respectively: wherein: R 1 and R 7 are independently hydrogen, hydrocarbyl, substituted hydrocarbyl, or —OR 111 ; R 5 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or —OR 511 ; R 6 is —OR 511 : R 2 is hydrogen, hydrocarbyl, substituted hydrocarbyl, halo, or —OR 211 ; R 3 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or —OR 311 ; R 4 is hydrogen, hydrocarbyl, substituted hydrocarbyl, halo, or —OR 411 ; R 66a and R 66b are independently selected from the group consisting of alkoxy and alkylthio or together with the carbon atom to which they are attached form a ketal, dithioketal, or monothioketal; R 12 is hydrogen, hydrocarbyl, substituted hydrocarbyl, halo, or —OR 121 ; R 13 is hydrogen, hydrocarbyl, substituted hydrocarbyl, halo, or —OR 511 ; R 111 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or a hydroxy protecting group; R 121 is hydrogen, hydrocarbyl, or substituted hydrocarbyl; R 211 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or a hydroxy protecting group; R 311 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or a hydroxy protecting group; R 411 is hydrogen, hydrocarbyl, substituted hydrocarbyl, or a hydroxy protecting group; R 511 is hydrogen, hydrocarbyl, substituted hydrocarbyl or a hydroxy protecting group; and —Z— is