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US 4,540,787 AGranted
Method of preparing trans-D1-1-alkyl-6-oxodecahydroquinolines
AssigneeEli Lilly and Company
InventorJohn M. Schaus
Life of this patent
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Abstract
A process for preparing 1-alkyl-6-oxodecahydroquinolines in 5 steps--a quaternization, hydrogenation, two organometallic reductions and hydrolysis of the thus formed enol ether--from 6-alkyloxyquinoline and intermediates useful therein.
Claims11
The synthetic method which comprises the steps of:
- A. quaternizing a 6-alkyloxyquinoline with a C.sub.1-3 alkyl halide or pseudo halide or with an allyl halide or pseudo halide in an inert mutual solvent to yield a quaternary salt of the formula ##STR3## 10 wherein R.sup.2 is C.sub.1-3 alkyl, R.sup.1 is R.sup.2 or allyl and X is a halogen or pseudo halogen;
- B. hydrogenating said quaternary salt in an inert mutual solvent under pressure using a noble metal catalyst to yield a tetrahydroquinoline salt of the formula ##STR4## wherein R and R.sup.2 are separately C.sub.1-3 alkyl and X has its previously assigned meaning;
- C. converting said HX salt to the corresponding free base with aqueous alkali;
- D. reducing said free base with an alkali metal in liquid ammonia, optionally in the presence of a second mutual inert solvent, to yield a mixture of N-alkyl hexahydroquinolines of the formulas ##STR5## wherein R and R.sup.2 have their previous meaning;
- E. reducing said hexahydroquinoline mixture with a borohydride in glacial acetic acid and a mutual inert solvent to yield a racemic mixture of octahydroquinolines of the formula ##STR6## F. treating said racemic mixture with acid in an inert mutual solvent to form a racemic mixture of 6-oxodecahydroquinolines of the formula ##STR7## G. and then isolating said racemate, or an acid addition salt thereof, in substantially pure form.
2 more elements
The synthetic method which comprises the steps of:
- A. hydrogenating 6-alkyloxyquinoline over a noble metal catalyst in an inert mutual solvent to yield a compound of the formula ##STR8## wherein R.sup.2 is C.sub.1-3 alkyl;
- B. alkylating said tetrahydroquinoline with an aldehyde R.sup.3 CHO wherein R.sup.3 is H, CH.sub.3 or C.sub.2 H.sub.5 in an inert mutual solvent under pressure using a noble metal catalyst to yield a tetrahydroquinoline of the formula ##STR9## wherein R and R.sup.2 are separately C.sub.1-3 alkyl;
- C. reducing said free base with an alkali metal in liquid ammonia, optionally in the presence of a second mutual inert solvent, to yield a mixture of N-alkyl hexahydroquinolines of the formulas ##STR10## wherein R and R.sup.2 have their previous meaning;
- D. reducing said hexahydroquinoline mixture with a borohydride in glacial acetic acid and a mutual inert solvent to yield a racemic mixture of octahydroquinolines of the formula ##STR11## E. treating said racemic mixture with acid in an inert mutual solvent to form a racemic mixture of 6-oxodecahydroquinolines of the formula ##STR12## F. and then isolating said racemate, or an acid addition salt thereof, in substantially pure form.
1 more element
Dependencies are inferred from the claim text.