Patent GB-1525891-A (GB)
Title: Prostaglandin intermediates
IPC: A61K31/343
Filed: 1977-01-04
Abstract: 1525891 Prostaglandin intermediates UPJOHN CO 4 Jan 1977 [2 Feb 1976] 00010/77 Heading C2C [Also in Division C3] The invention comprises a process for preparing prostaglandin intermediates of the Formula VII wherein n is 1 or 2; R 1  is H, CH 3  or CH 3 CH 2 ; and R 4  is (1) hydrogen, (2)-2-tetrahydropyranyl; (3) 2-tetrahydrofuranyl, (4) wherein R 6  is C 1-18  alkyl, C 3-10  cycloalkyl, C 7-12  aralkyl or phenyl optionally substituted with 1 to 3 C 1-4  alkyls; R 7  and R 8  each or 11, C 1-4  alkyl, or phenyl optionally substituted by 143 C 1-4  alkyls, or R 7  and R 8  together are (CH 2 )a, (CH 2 )bO-(CH 2 )c, wherein a is 3 2  to 5, b is 1 to 3 and c is 1 to 3, with the proviso that b + c is 2 to 4, and Ra is H or phenyl; (5) optionally substituted benzoyl or naphthoyl or C 2À2  alkanoyl; by (a) reacting tricyclic aldehydes of the Formula VIII with the ylids derived from phosphonium bromides of the formula to form alkenes of the Formula IX (b) hydroxylating products of step (a) to form glycols of the Formula X (3) converting glycols of step (b) to compounds of the Formula XI where R 2  is C 1-19  alkyl or C 7-12  aralkyl optionally substituted with 1 to 3 halogen atoms, by stepwise reaction with (1) ortho esters of the formula wherein R 5  is CH 3  or CH 2 CH 3 , and (2) anhydrous formic acid; (d) removing the formyl groups from the production of step (c) by solvolysis in the presence of bases; (e) reacting the products of step (d) with 2,3-dihydropyron, 2,3-dihydrofuron or ethers of the formula in the presence of acid condensing agents, to form compounds of the Formula XII wherein R 3  is 2-tetrahydropyranyl, 2-tetrahydro furanyl or a group of the formula (f) replacing the -COR 2  groups in the products of step (e) with H by solvolysis in the presence of bases to form compounds of the Formula XIII (g) oxidizing the free hydroxyl groups of the products of step (f) to form compound of Formula VII above in which R 4  and R 3  and optionally (h) replacing R 3  in products of step (g) with H by acid hydrolysis; and, optionally (i) reacting the products of step (h) with acid anhydrides or acyl chlorides in the presence of tertiary amines to form compounds of Formula VII above in which R 4  is carboxyacyl; and the compounds of the Formula VII above the proviso that if R 4  is as defined above for any of the groups (2), (3) and (4), then n is 2. The following compounds are also prepared: endo - 6 - (2 - ethoxy - 2 - ethyl - 1,3 - dioxen - 2 - yl) - exo - 3 - hydroxy [3,1,0]hexan - exo - 2 - acetic acid, γ - lactone; 5α - hydroxy - 3α - (tetrahydro - 2H - pyran - 2 - yloxy) - 2# - (3α - hydroxy - 4,4 - dimethyl - trans - 1 - octenyl) - 1α - cyclopentaneacetic acid, γ - lactone; 5α - hydroxy - 3α - (tetrahydro - 2H - pyran - 2 - yloxy) - 2# - (3α - hydroxy - trans - 1 - acetenyl) - 1α - cyclopentaneacetic acid, γ - lactone; 5α - hydroxy - 3α - (tetrahydro - 2H - pyran - 2 - yloxy) - 2# - (3α - hydroxy - trans - 1,cis - 5 - octadienyl) - 1α - cyclopentaneacetic acid, γ- lactone; the lactols corresponding to the lactones of Formula IX above; and 2 - (3 - methoxy- 2 - propenyl) - 6 - vinylbicyclo[3,1,0] - hexan -  3 - ol.