Resolution process and salt of protected D-penicillamine and L-pseudonorephedrine

Claim 2

The optically active salt of a protected D-form of penicillamine and l-pseudonoresphedrine where the protected penicillamine has the formula ##EQU4## where Ac is benzoyl, tosyl, nitrophenyl-sulfenyl, formyl, acetyl or propionyl, R is hydrogen, benzyl or Ac, R 1 and R 2 are hydrogen, alkyl of 1 to 8 carbon atoms, cycloalkyl of 5 to 8 carbon atoms, phenyl or tolyl or R 1 and R 2 together with the adjacent carbon atoms of the thiazoline ring form a cycloalkylene ring of 5 to 8 carbon atoms and Z is hydrogen or together with Ac is phthaloyl.

Claim 3

The optically active salt according to claim 1 having formula II wherein Ac is acetyl or formyl and R 1 and R are each methyl or R 1 and R 2 together with the adjacent carbon atom are cyclopentamethylene.

Claim 4

A compound according to claim 1 having formula I.

Claim 5

A compound according to claim 3 wherein Ac is formyl, acetyl or propionyl and Z is hydrogen.

Claim 6

A compound according to claim 4 wherein Ac is formyl.

Claim 7

A compound according to claim 5 wherein R is benzyl.

Claim 8

A compound according to claim 1 having formula II.

Claim 9

A compound according to claim 7 wherein R 1 and R 2 are alkyl of 1 to 8 carbon atoms, cycloalkyl of 5 to 8 carbon atoms, phenyl or tolyl or R 1 and R 2 together with the adjacent carbon atom are cycloalkylene of 5 to 8 carbon atoms.

Claim 10

A compound according to claim 8 wherein Ac is formyl, acetyl or propionyl.

Claim 11

A compound according to claim 8 wherein Ac is formyl or acetyl and R 1 and R 2 are both alkyl.

Claim 12

A compound according to claim 10 wherein Ac is formyl.

Claim 13

A compound according to claim 11 wherein R 1 and R 2 are both methyl.

Claim 14

A compound according to claim 1 of formula II wherein R 1 and R 2 together with the adjacent carbon atom is cycloalkylene of 5 to 8 carbon atoms.

Claim 15

A compound according to claim 13 wherein Ac is formyl or acetyl and the cycloalkylene is cyclopentamethylene.

Claim 16

In a process of recovering the optically active salt of a protected D-form of penicillamine and an optically active base wherein the protected D-form of penicillamine has formula I or II according to claim 1 including the step of crystallizing out of solution in a solvent which comprises water, an alkanol, an aliphatic hydrocarbon, a halogenated aliphatic hydrocarbon, dioxane, a ketone, a carboxylic acid ester or an aromatic hydrocarbon of the salt of said protected penicillamine having formula I or II with an optically active base, the improvement comprising employing the D,L form of said protected penicillamine and l-pseudonorephedrine and preferentially precipitating the salt of the D form of said protected penicillamine of formula I or II with said l-pseudonorephedrine.

Claim 17

A process according to claim 15 wherein the protected penicillamine has formula II and R 1 and R 2 together with the adjacent carbon atom is cycloalkylene of 5 to 6 carbon atoms.

Claim 18

A process according to claim 16 wherein Ac is formyl and the cycloalkylene is cyclopentamethylene.

Claim 19

A process according to claim 15 wherein the solvent comprises an alkanol, an aliphatic hydrocarbon, halogenated aliphatic hydrocarbon, dioxane, a ketone, a carboxylic acid ester or an aromatic hydrocarbon.

Claim 20

A process according to claim 18 wherein the solvent is an alkanol of 1 to 3 carbon atoms or dioxane.

Claim 21

A process according to claim 15 wherein there is used 0.1 to 3 moles of l-pseudonorephedrine per mole of D,L-racemate of the protected penicillamine.

Claim 22

A process according to claim 20 wherein there is used 0.5 to 1.1 moles of l-pseudonorephedrine per mole of the D,L-racemate.

Claim 23

A process according to claim 15 wherein the protected penicillamine has formula I.

Claim 24

A process according to claim 22 wherein Ac is formyl or acetyl, Z is hydrogen and R is hydrogen or benzyl.

Claim 25

A process according to claim 15 wherein the protected pencillamine has formula II.

Claim 26

A process according to claim 24 wherein R 1 and R 2 are alkyl of 1 to 8 carbon atoms, cycloalkyl of 5 to 8 carbon atoms, phenyl or tolyl or R 1 and R 2 together with the adjacent carbon atom are cycloalkylene of 5 to 8 carbon atoms.

Claim 27

A process according to claim 25 wherein Ac is formyl or acetyl.

Claim 28

A process according to claim 26 wherein R 1 and R 2 are both alkyl.

Claim 29

A process according to claim 27 wherein Ac is formyl.

Claim 30

A process according to claim 28 wherein R 1 and R 2 are both methyl.