Hydrogenation process for the formation of 3,4-dihydro HMG-CoA reductase inhibitors

Claim 2

A process for the preparation of a compound of structural formula (IV): ##STR4## wherein: R 1 is H or C 1-3 alkyl; R 2 is H or C 1-3 alkyl; R 3 is C 1-5 alkyl, phenyl, or C 3-7 cycloalkyl; or C 1-5 alkyl or phenyl substituted with a group Y where Y is selected from the group consisting of: (a) OH or t-C 4 H 9 (Me) 2 SiO; (b) halogen; (c) trifluoromethyl; (d) C 1-3 alkoxy; (e) C 1-3 alkylcarbonyloxy; (f) phenylcarbonyloxy; (g) C 1-3 alkoxycarbonyl; or (h) phenyloxycarbonyl; R 4 is H or CH 3 or CH 2 OH or OH or CH 2 OSi(Me) 2 t-C 4 H 9 or OSi(Me) 2 t-C 4 H 9 ; R 5 is H or CH 2 OH or OH or CH 2 OSi(Me) 2 t-C 4 H 9 or OSi(Me) 2 t-C 4 H 9 ; provided that when either R 4 or R 5 is CH 2 OH or CH 2 OSi(Me) 2 t-C 4 H 9 the other is H; and one and only one of R 4 and R 5 can be OH or OSi(Me) 2 t-C 4 H 9 . a is a double bond or a single bond; which comprises: contacting of a compound of structural formula (IIi): ##STR5## with Rh(Ar 3 P) 3 X; wherein Ar is phenyl or naphthyl or C 1-3 alkoxy substituted phenyl or naphthyl; X is Cl or Br; in an alcoholic solvent, under hydrogen gas at a pressure of 40-1400 psi at a temperature of 40°-80° C.

Claim 3

A process of claim 1 wherein the alcoholic solvent is a mixture of isopropanol or ethanol and a hydrocarbon such as benzene or toluene.

Claim 4

A process of claim 2 wherein the alcoholic solvent is isopropanol, or ethanol.

Claim 5

A process of claim 3 wherein the Rhodium Catalyst is Rh(Ph 3 P) 3 Cl.

Claim 6

A process of claim 4 wherein the weight percent ratio of catalyst to substrate (III) is about 5 weight percent.

Claim 7

A process of claim 5 wherein the hydrogen gas is at a pressure of about 600-1400 psi.

Claim 8

A process of claim 1 wherein R 4 is H or CH 3 or CH 2 OH or CH 2 OSi(Me) 2 t-C 4 H 9 ; R 5 is H or CH 2 OH or CH 2 OSi(Me) 2 t-C 4 H 9 ; provided that at least one of R 4 or R 5 is H.

Claim 9

A process of claim 1 wherein: R 1 is CH 3 , R 2 is H or CH 3 , R 3 is C 1-5 alkyl, R 4 is CH 3 , R 5 is H, a is a double bond.

Claim 10

A process of claim 8 wherein: R 2 is H and R 3 is CH 3 CH 2 .

Claim 11

A process of claim 8 wherein: R 2 is CH 3 and R 3 is CH 3 CH 2 .

Claim 12

A process of claim 1 wherein: R 1 is CH 3 , R 2 is H or CH 3 , R 3 is C 1-5 alkyl, R 4 is H or CH 2 OH or CH 2 OSi(Me) 2 t-C 4 H 9 , R 5 is H or CH 2 OH or CH 2 OSi(Me) 2 t-C 4 H 9 ; and a is a double bond.

Claim 13

A process of claim 11 wherein the compound (IV) prepared is selected from the group wherein: ______________________________________ a. R.sub.2 is H, e. R.sub.2 is H, R.sub.3 is CH.sub.3 CH.sub.2, R.sub.3 is CH.sub.3 CH.sub.2, R.sub.4 is CH.sub.2 OH, R.sub.4 is CH.sub.2 OSi(Me).sub.2 t-C.sub.4 H.sub.9, R.sub.5 is H; R.sub.5 is H; b. R.sub.2 is H, f. R.sub.2 is H, R.sub.3 is CH.sub.3 CH.sub.2, R.sub.3 is CH.sub.3 CH.sub.2, R.sub.4 is H, R.sub.4 is H, R.sub.5 is CH.sub.2 OH; R.sub.5 is CH.sub.2 OSi(Me).sub.2 t-C.sub.4 H.sub.9 ; c. R.sub.2 is CH.sub.3, g. R.sub.2 is CH.sub.3, R.sub.3 is CH.sub.3 CH.sub.2, R.sub.3 is CH.sub.3 CH.sub.2, R.sub.4 is CH.sub.2 OH, R.sub.4 is CH.sub.2 OSi(Me).sub.2 t-C.sub.4 H.sub.9, R.sub.5 is H; R.sub.5 is H; d. R.sub.2 is CH.sub.3, h. R.sub.2 is CH.sub.3, R.sub.3 is CH.sub.3 CH.sub.2, R.sub.3 is CH.sub.3 CH.sub.2, R.sub.4 is H, R.sub.4 is H, R.sub.5 is CH.sub.2 OH. R.sub.5 is CH.sub.2 OSi(Me).sub.2 t-C.sub.4 H.sub.9. ______________________________________

Claim 14

A process of claim 1 wherein: R 1 is CH 3 , R 2 is H or CH 3 , R 3 is H or CH 3 or OH or OSi(Me) t -C 4 H 9 , R 5 is H or OH or OSi(Me) 2 t-C 4 H 9 ; provided that one and only one of R 4 and R 5 is OH or OSi(Me) 2 t-C 4 H 9 .

Claim 15

A process of claim 13 wherein R 3 is C 1-3 alkyl.

Claim 16

A process of claim 14 wherein R 3 is CH 3 CH 2 .

Claim 17

A process of claim 15 wherein the compound (IV) prepared is selected from the group wherein: a. R 2 is H, R 4 is OH and R 5 is H; b. R 2 is CH 3 , R 4 is OH and R 5 is H; c. R 2 is H, R 4 is H and R 5 is OH; d. R 2 is H, R 4 is CH 3 and R 5 is OH; e. R 2 is CH 3 , R 4 is H and R 5 is OH; f. R 2 is CH 3 , R 4 is CH 3 and R 5 is OH. g. R 2 is H, R 4 is OSi(Me) 2 t-C 4 H 9 and R 5 is H; h. R 2 is CH 3 , R 4 is OSi(Me) 2 t-C 4 H 9 and R 5 is H; i. R 2 is H, R 4 is H and R 5 is OSi(Me) 2 t-C 4 H 9 ; j. R 2 is H, R 4 is CH 3 and R 5 is OSi(Me) 2 t-C 4 H 9 ; k. R 2 is CH 3 , R 4 is H and R 5 is OSi(Me) 2 t-C 4 H 9 ; l. R 2 is CH 3 , R 4 is CH 3 and R 5 is OSi(Me) 2 t-C 4 H 9 .

Claim 18

A process of claim 9 wherein the alcoholic solvent is isopropanol, the catalyst is tris(triphenylphosphine)rhodium (I) chloride at a weight percent ratio of 5 percent catalyst to substrate (III), under a hydrogen gas pressure of about 1400 psi at a temperature of about 40° C.

Claim 19

A process of claim 10 wherein the alcoholic solvent is isopropanol, th catalyst is tris(triphenylphosphine)rhodium (I) chloride at a weight percent ratio of 5 percent catalyst to substrate (III), under a hydrogen gas pressure of about 1400 psi at a temperature of about 40° C.

Claim 20

A process of claim 12 wherein the alcoholic solvent is isopropanol, the catalyst is tris(triphenylphosphine)rhodium (I) chloride at a weight percent ratio of 5 percent catalyst to substrate (III), under a hydrogen gas pressure of about 1400 psi at a temperature of about 40° C.

Claim 21

A process of claim 16 wherein the alcoholic solvent is isopropanol, the catalyst is tris(triphenylphosphine)rhodium (I) chloride at a weight percent ratio of 5 percent catalyst to substrate (III), under a hydrogen gas pressure of about 1400 psi at a temperature of about 40° C.