9-Oxobenzomorphan process
AssigneeBristol-Myers Company
InventorGerry Kavadias
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Abstract
Improved processes for preparing 2'-alkoxy-2,5-di-substituted-9-oxo-6,7-benzomorphans from benz[e]indolines and synthesis of the benz[e]indoline intermediates are described. A representative example involves synthesis of 9b-allyl-8-methoxy-3-methyl-5,9b-dihydrobenz[e]indoline and bromination thereof to 9b-allyl-4-bromo-8-methoxy-2,4,5,9b-tetrahydro-1H-benz[e]indole methylbromide which is then hydrolyzed with a weak base such as ammonium bicarbonate to provide 5-allyl-2'-methoxy-2-methyl-9-oxo-6,7-benzomorphan.
Claims13
A process for preparing 2'-alkoxy-2,5-di-substituted-9-oxo-6,7-benzomorphan compounds of formula I ##STR106## wherein R.sub.1 is lower alkyl of 1 to 4 carbon atoms inclusive or benzyl;
- R.sub.2 is lower alkyl of 1 to 4 carbon atoms inclusive, allyl, benzyl, or ##STR107## R.sub.3 is lower alkyl of 1 to 4 carbon atoms inclusive, ##STR108## in which R.sub.4 is hydrogen or methyl;
- which comprises sequential steps of,
- (a) brominating a dihydroben[e]indoline of formula II ##STR109## in which R.sub.1, R.sub.2, and R.sub.3 are as recited above wherein said bromination is carried out by combining a methylene chloride solution of the formula II compound and a solution of bromine in methylene chloride at a temperature in the range of -40.degree. to -70.degree. to produce a bromoenaminium bromide compound have formula III ##STR110## in which R.sub.1, R.sub.2, and R.sub.3 are as recited above;
- (b) treating the formula III compound with a bicarbonate base selected from the group consisting of potassium bicarbonate, sodium bicarbonate, and ammonium bicarbonate for activated aluminum oxide to produce the 9-oxo-6,7-benzomorphan compound of formula I.
Dependencies are inferred from the claim text.