11-Substituted hexahydro-2,6-methano-3-benzazocines

Claim 2

A compound having the formula ##STR48## where R 1 is hydrogen, lower-alkyl, lower-alkanoyl (only when R 4 is hydrogen), lower-alkenyl, lower-alkynyl, halo-lower-alkenyl, cyclo-lower-alkyl, cyclo-lower-alkyl-lower-alkyl, 2- or 3-furylmethyl, or such 2- or 3-furylmethyl substituted on the unsubstituted ring carbon atoms by from one to three methyl groups, phenyl-lower-alkyl, or phenyl-lower-alkyl substituted in the phenyl ring by from one to two members of the group consisting of halogen, lower-alkyl, hydroxy, lower-alkanoyloxy, lower-alkoxy, lower-alkylmercapto, trifluoromethyl, amino, lower-alkanoylamino or a single methylenedioxy attached to adjacent carbon atoms; R 2 , R 2 ', R 2 " and R 2 '" are each hydrogen, or three of them are hydrogen and the fourth is halogen, lower-alkyl, hydroxy, lower-alkanoyloxy, lower-alkoxy, lower-alkylmercapto, trifluoromethyl, nitro, amino, lower-alkanoylamino, lower-alkoxycarbonylamino or phenyl, or two of the adjacent such groups together are methylenedioxy; R 3 is hydrogen or lower-alkyl; R 4 is hydrogen, lower-alkyl, lower-alkoxy-lower-alkyl, hydroxy-lower-alkyl, lower-alkylthio-lower-alkyl, lower-alkylsulfinyl-lower-alkyl, phenylthio-lower-alkyl, phenylsulfinyl-lower-alkyl, lower-alkenyl or halolower-alkyl, or R 3 and R 4 together are divalent lower-alkylene, --(CH 2 ) n --, where n is one of the integers 3 or 4; and Z is the group ##STR49## or the ethylene glycol ketal thereof, where R 5 is hydrogen, lower-alkyl, cyclo-lower-alkyl-lower-alkyl, phenyl or phenyl-lower-alkyl; and R 8 is hydrogen or lower-alkyl; or an acid-addition salt thereof.

Claim 3

A compound having the formula ##STR50## where R 1 is hydrogen, lower-alkyl, lower-alkenyl, lower-alkynyl, halo-lower-alkenyl, cyclo-lower-alkyl-lower-alkyl, 2- or 3-furylmethyl, or such 2- or 3-furylmethyl substituted on the unsubstituted ring carbon atoms by from one to three methyl groups, or phenyl-lower-alkyl; R 2 is hydrogen, hydroxy or lower-alkoxy; R 3 is hydrogen or lower-alkyl; R 4 is lower-alkyl or lower-alkoxy-lower-alkyl, or R 3 and R 4 together are divalent lower-alkylene, --(CH 2 ) n --, where n is one of the integers 3 or 4; Z is the group --CH 2 COR 5 , where R 5 is hydrogen, lower-alkyl, cyclo-lower-alkyl-lower-alkyl, phenyl, phenyl-lower-alkyl; or an acid-addition salt thereof.

Claim 4

A compound having the formula ##STR50## where R 1 is hydrogen, lower-alkyl, lower-alkenyl, lower-alkynyl, halo-lower-alkenyl, cyclo-lower-alkyl-lower-alkyl, 2- or 3-furylmethyl, or such 2- or 3-furylmethyl substituted on the unsubstituted ring carbon atoms by from one to three methyl groups, or phenyl-lower-alkyl; R 2 is hydrogen, hydroxy or lower-alkoxy; R 3 is hydrogen or lower-alkyl; R 4 is lower-alkyl or lower-alkoxy-lower-alkyl, or R 3 and R 4 together are divalent lower-alkylene, --(CH 2 ) n --, where n is one of the integers 3 or 4; Z is the group --CH 2 COR 5 , where R 5 is hydrogen, lower-alkyl, cyclo-lower-alkyl-lower-alkyl, phenyl, phenyl-lower-alkyl; or an acid-addition salt thereof.

Claim 5

A compound according to claim 2 where R 5 is lower-alkyl.

Claim 6

6(eq)-Ethyl-1,2,3,4,5,6-hexahydro-3-methyl-11(eq)-(3-oxobutyl)-2,6-methano-3-benzazocine according to claim 3.

Claim 7

6(eq)-Ethyl-1,2,3,4,5,6-hexahydro-3,11(ax)-dimethyl-11(eq)-(3-oxobutyl)-2,6-methano-3-benzazocine according to claim 3.

Claim 8

3-Cyclopropylmethyl-6(eq)-ethyl-1,2,3,4,5,6-hexahydro-11(eq)-(3-oxobutyl-2,6-methano-3-benzazocine according to claim 3.

Claim 9

6(eq)-Ethyl-1,2,3,4,5,6-hexahydro-8-hydroxy-3-methyl-11(eq)-(3-oxobutyl)-2,6-methano-3-benzazocine according to claim 3.

Claim 10

3-Cyclopropylmethyl-8-hydroxy-6(eq)-methyl-1,2,3,4,5,6-hexahydro-11(eq)-(3-oxobutyl)-2,6-methano-3-benzazocine according to claim 3.

Claim 11

3,6(eq)-Dimethyl-8-hydroxy-1,2,3,4,5,6-hexahydro-11(eq)-(3-oxobutyl)-2,6-methano-3-benzazocine according to claim 3.

Claim 12

3-Cyclopropylmethyl-8-methoxy-6(eq)-methyl-1,2,3,4,5,6-hexahydro-11(eq)-(3-oxobutyl)-2,6-methano-3-benzazocine according to claim 3.

Claim 13

3,6(eq)-Dimethyl-8-methoxy-1,2,3,4,5,6-hexahydro-11(eq)-(3-oxooctyl)-2,6-methano-3-benzazocine according to claim 3.

Claim 14

3,6(eq)-Dimethyl-8-hydroxy-1,2,3,4,5,6-hexahydro-11(eq)-(3-oxooctyl)-2,6-methano-3-benzazocine according to claim 3.

Claim 15

A compound according to claim 3 where R 1 , R 3 and R 4 are each lower-alkyl; and R 2 is hydroxy.

Claim 16

3,6(eq),11(ax)-Trimethyl-8-hydroxy-1,2,3,4,5,6-hexahydro-11(eq)-(3-oxooctyl)-2,6-methano-3-benzazocine according to claim 13.

Claim 17

3,6(eq),11(ax)-Trimethyl-8-hydroxy-1,2,3,4,5,6-hexahydro-11(eq)-(3-oxoheptyl)-2,6-methano-3-benzazocine according to claim 13.

Claim 18

3,6(eq),11(ax)-Trimethyl-8-hydroxy-1,2,3,4,5,6-hexahydro-11(eq)-(3-oxo-6-methylheptyl)-2,6-methano-3-benzazocine according to claim 13.

Claim 19

3,6(eq),11(ax)-Trimethyl-8-hydroxy-1,2,3,4,5,6-hexahydro-11(eq)-(3-oxobutyl)-2,6-methano-3-benzazocine according to claim 13.

Claim 20

A compound according to claim 2 where R 5 is cyclo-lower-alkyl-lower-alkyl.

Claim 21

A compound according to claim 18 where R 1 , R 3 and R 4 are each lower-alkyl; and R 2 is hydroxy.

Claim 22

3,6(eq),11(ax)-Trimethyl-8-hydroxy-1,2,3,4,5,6-hexahydro-11(eq)-(3-oxo-5-cyclopropylpentyl)-2,6-methano-3-benzazocine according to claim 19.

Claim 23

3,6(eq),11(ax)-Trimethyl-8-hydroxy-1,2,3,4,5,6-hexahydro-11(eq)-(3-oxo-5-cyclopentylpentyl)-2,6-methano-3-benzazocine according to claim 19.

Claim 24

A compound according to claim 2 where R 5 is phenyl-lower-alkyl.

Claim 25

A compound according to claim 22 where R 1 , R 3 and R 4 are each lower-alkyl; and R 2 is hydroxy.

Claim 26

3,6(eq),11(ax)-Trimethyl-8-hydroxy-1,2,3,4,5,6-hexahydro-11(eq)-(3-oxo-5-phenylpentyl)-2,6-methano-3-benzazocine according to claim 23.

Claim 27

A compound having the formula ##STR51## where R 1 , R 3 and R 4 are each lower-alkyl; R 2 is methoxymethoxy; and Z is CH 2 COR 5 , where R 5 is lower-alkyl; or an acid-addition salt thereof.

Claim 28

A compound having the formula ##STR51## where R 1 , R 3 and R 4 are each lower-alkyl; R 2 is methoxymethoxy; and Z is CH 2 COR 5 , where R 5 is lower-alkyl; or an acid-addition salt thereof.

Claim 29

3,6(eq),11(ax)-Trimethyl-8-methoxymethoxy-1,2,3,4,5,6-hexahydro-11(eq)-(3-oxooctyl)-2,6-methano-3-benzazocine according to claim 25.

Claim 30

The process for preparing a compound according to claim 1 having the formula ##STR52## where R 1 is hydrogen, lower-alkyl, lower-alkanoyl (only when R 4 is hydrogen), lower-alkenyl, lower-alkynyl, halo-lower-alkenyl, cyclo-lower-alkyl, cyclo-lower-alkyl-lower-alkyl, 2- or 3-furylmethyl, or such 2- or 3-furylmethyl substituted on the unsubstituted ring carbon atoms by from one to three methyl groups, phenyl-lower-alkyl, or phenyl-lower-alkyl substituted in the phenyl ring by from one to two members of the group consisting of halogen, lower-alkyl, hydroxy, lower-alkanoyloxy, lower-alkoxy, lower-alkylmercapto, trifluoromethyl, amino, lower-alkanoylamino or a single methylenedioxy attached to adjacent carbon atoms; R 2 , R 2 ', R 2 " and R 2 "' are each hydrogen, or three of them are hydrogen and the fourth is halogen, lower-alkyl, hydroxy, lower-alkanoyloxy, lower-alkoxy, lower-alkylmercapto, trifluoromethyl, nitro, amino, lower-alkanoylamino, lower-alkoxycarbonylamino or phenyl, or two of the adjacent such groups together are methylenedioxy; R 3 is hydrogen or lower-alkyl; R 4 is hydrogen, lower-alkyl, lower-alkoxy-lower-alkyl, hydroxy-lower-alkyl, lower-alkylthio-lower-alkyl, lower-alkylsulfinyl-lower-alkyl, phenylthio-lower-alkyl, phenylsulfinyl-lower-alkyl, lower-alkenyl or halo-lower-alkyl, or R 3 and R 4 together are divalent lower-alkylene, --(CH 2 ) n --, where n is one of the integers 3 or 4; and Z is the group ##STR53## or the ethylene glycol ketal thereof, where R 5 is hydrogen, lower-alkyl, cyclo-lower-alkyl-lower-alkyl, phenyl or phenyl-lower-alkyl: and R 8 is hydrogen or lower-alkyl, which comprises heating, with formic acid in an inert organic solvent or with a benzyl-di-lower-alkylammonium or tri-lower-alkylammonium formate, a compound having the formula ##STR54## where Y is COR 5 and R 1 , R 2 , R 2 ', R 2 ", R 2 "', R 3 , R 4 , R 5 and R 8 have the meanings given above.