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US4308378A
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Cis/trans isomerization of 6-(substituted-aryl-ethenyl)-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-ones
Assignee: Merck and Co Inc
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Filing: 1980-09-02
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Granted: 1981-12-29
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Expires: 2000-09-02
Abstract
Abstract Biologically inactive cis-6-(substituted-arylethenyl)-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-ones are isomerized to the corresponding anti-hypercholesterolemic trans-isomers by heating in the presence of a heavy metal salt.
Inventors
- 👤 Gerald E. Stokker
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-25 11:20
CPC Classifications
C; C07; C07D; C07D263/00; C07D263/02; C07D263/08; C07D263/10; C07C; C07C45/00; C07C45/51; C07C45/511; C07C45/512; C07C45/516; C07C45/56; C07C45/61; C07C45/67; C07C45/68; C07C45/70; C07C45/71; C07C45/72; C07C45/74; C07C47/00; C07C47/20; C07C47/277; C07C47/52; C07C47/55; C07C47/575; C07C59/00; C07C59/40; C07C59/58; C07C59/64; C07C59/66; C07D309/00; C07D309/16; C07D309/28; C07D309/30; C07F; C07F15/00; C07F15/0006; C07F15/006
Claims Analysis
Total Claims: 7
Claim 1
Independent Claim
191 words
A process for the preparation of the transisomer of the compound with structural formula: ##STR8## wherein R 1 , R 2 and R 3 are each selected from (a) hydrogen, (b) halogen, (c) C 1-4 alkyl, (d) C 1-4 haloalkyl, (e) phenyl, (f) phenyl substituted by (1) halogen, (2) C 1-4 alkoxy, (3) C 2-8 alkanoyloxy, (4) C 1-4 alkyl, or (5) C 1-4 haloalkyl, and (g) OR 4 in which R 4 is (1) hydrogen, (2) C 2-8 alkanoyl, (3) benzoyl, (4) phenyl, (5) halophenyl (6) phenyl C 1-3 alkyl, (7) C 1-9 alkyl, (8) cinnamyl, (9) C 1-4 haloalkyl, (10) allyl, (11) cycloalkyl-C 1-3 alkyl, (12) adamantyl-C 1-3 alkyl, or (13 ) substituted phenyl-C 1-3 alkyl in each of which the substituents are selected from (i) halogen, (ii) C 1-4 alkoxy, (iii) C 1-4 alkyl, or (iv) C 1-4 haloalkyl; which comprises heating in an aqueous inert organic solvent in the presence of a heavy metal salt derived from a cation of a metal selected from mercury, zinc, lead, and cadmium and an anion selected from bromide, chloride, fluoride, iodide, nitrate and sulfate, the corresponding cis-isomer of structure: ##STR9##
Claim 2
Dependent Claim
191 words
A process for the preparation of the transisomer of the compound with structural formula: ##STR8## wherein R 1 , R 2 and R 3 are each selected from (a) hydrogen, (b) halogen, (c) C 1-4 alkyl, (d) C 1-4 haloalkyl, (e) phenyl, (f) phenyl substituted by (1) halogen, (2) C 1-4 alkoxy, (3) C 2-8 alkanoyloxy, (4) C 1-4 alkyl, or (5) C 1-4 haloalkyl, and (g) OR 4 in which R 4 is (1) hydrogen, (2) C 2-8 alkanoyl, (3) benzoyl, (4) phenyl, (5) halophenyl (6) phenyl C 1-3 alkyl, (7) C 1-9 alkyl, (8) cinnamyl, (9) C 1-4 haloalkyl, (10) allyl, (11) cycloalkyl-C 1-3 alkyl, (12) adamantyl-C 1-3 alkyl, or (13 ) substituted phenyl-C 1-3 alkyl in each of which the substituents are selected from (i) halogen, (ii) C 1-4 alkoxy, (iii) C 1-4 alkyl, or (iv) C 1-4 haloalkyl; which comprises heating in an aqueous inert organic solvent in the presence of a heavy metal salt derived from a cation of a metal selected from mercury, zinc, lead, and cadmium and an anion selected from bromide, chloride, fluoride, iodide, nitrate and sulfate, the corresponding cis-isomer of structure: ##STR9##
Claim 3
Dependent Claim
80 words
The process of claim 1, wherein R 1 , R 2 and R 3 are each selected from (a) halogen, (b) C 1-4 alkyl, (c) C 1-4 haloalkyl, (d) phenyl or substituted phenyl in which the substituent is (1) halo, (2) C 1-4 alkyl, (3) C 1-4 alkoxy, and (e) OR 4 in which R 4 is (1) phenyl, (2) halophenyl, or (3) substituted phenyl-C 1-3 alkyl wherein the substituents are selected from (i) halogen, and (ii) C 1-4 haloalkyl.
Claim 4
Dependent Claim
37 words
The process of claim 1 wherein R 1 is in the 6-position and is halophenyloxy, halophenylalkoxy or halophenyl, where halo is fluoro or chloro; and R 2 and R 3 are halo in the 2 and 4-positions.
Claim 5
Dependent Claim
23 words
The process of claim 1 wherein R 1 is 6-(4-fluorophenyl) or 6-(4-(chlorophenyl) and R 2 and R 3 are 2-chloro and 4-chloro respectively.
Claim 6
Dependent Claim
36 words
The process of claims 1, 2 3 or 4 wherein the isomerization is conducted at 50°-200° C., for 40-100 hours in aqueous acetonitrile in relative volumes of 1:1 to 1:10 in the presence of mercuric chloride.
Claim 7
Dependent Claim
34 words
The process of claims 1, 2, 3 or 4 wherein the isomerization is conducted at 75°-125° C. for 60-76 hours in aqueous acetonitrile in relative volumes of 1:5 in the presence of mercuric chloride.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1984-12-28 | 1985-06-29 | 1985-12-29 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1988-12-28 | 1989-06-29 | 1989-12-29 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1992-12-28 | 1993-06-29 | 1993-12-29 | $7700.00 | Window Closed / Lapsed |