CA1069504A - Cyclopentane derivatives and process for their manufacture - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
Novel 3-oxo-1-alkenyl-2-oxo-bicyclo[3,3,0]octan-3-ones and 3-oxo-1-alkanyl-2-oxo-bicyclo[3,3,0]octan-3-ones prepared by reacting an aldehyde with a phosphorane or a phosphonate are useful as intermediates for producing prostaglandin derivatives.

Description

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The pre~ent in~ention ~s concer~ed with nsw cyclopentane dlerivative~ and with their ma~u~acture and u3eO
The present inventlon provides compounds oi the ge~eral iormula I

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O
~2 , in whi¢h B represents a -oH2-C~2- or a tran~ -o~E- group, represents a methyl or ethyl group and 0~ repres~nt~ a hydroxyl group, a~ acylo~y group or an etheriiied hydro~yl group.
~ etherii~ed hydroxyl group~ and acyloxy group~ represented by ~ there come into consideration group~ kno~n to the e~pert.
Preierred etheriiied hydro~yl group~ are tho~e that can be aplit oii ea~ily cr under mild conditio~; thero may be mentioned b~
way oi example tetrah~dropyranyl, tetrahydro~uranyl, a-etho~yethyl, tr~methyl~ tr~-para-~ylyl-æilyl and dimethyl-tertO-butyl-silyl group~O There ma~ be mentioned a~ a~ylo~y groups those in which the acyl group~ pre~erably contain up to 15 carbon atoms, pre~erably ac~tyl, propio~yl, butyryl, ben~oyl and paraphenyl-ben20yl group~.

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The pre~ent inventio~ al~o provides a proces~ ~or ~he ma~u~acture o~ the compound~ o~ the general ~ormula I, wh~rein an alde~yde o~ the general ~ormula II

in which O~ repre~ent~ an acylogy group or an etheri~ied hydro~yl group, i~ reacted ~7ith a pho~phorane of the general formula III

- (c6H5~3p=o~ C ~ (III) 9 in which Rl ha~ the meaning given above, or wlth a pho~pho~ate oi the general iormula IV
O O
( ~ 0)2P--~H2~

in wh~ch ~ ha3 the meani~g given above, and, li de3ired, ln the re~ulting compound the carbon-to-oarbon tran~ double bond i~
hydrogenated to form a ~ k~ carbon-to-carbon ~ingle bond a~d/or the acylo~y group or th~ etheriiied hydroxyl group iB ~o~verted into a ~ree hydro~yl groupO
~ he etep or steps in the pro¢ess oi the present inventio~
may be carried out ln a known mannerO

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The reaction with the pho~phorane may be e~ected iQ a m~ner known ~E ~e ~n an l~ert solvent9 ~or example be~ene, toluene, xylene, diet~yl ether, tetrahydro~uran, dioxan, chloro~orm, di~ethyl ~ulpho~ide, methylene chloride or dimethyl~ormamide, at a temperature wlthin the range of ~ro~ 0C to 100a, preferably at 25C. ~he reaction with a phosphonate may b~ carried out i~
th~ presence o~ a cataly~t, ior e~ample butyl llthium or ~odium hydrid~, in a sol~ent, *or exa~ple dimetho~yeth~ne, diethyl ether, t~trahydro~uran or dioxa~, at a temperature ~ithin the range o~
~rom ~oa to -70C, pre~erably -20C to 0C0 When B represents a -CE2-oH2- group in the de~ired end product, the carbon-to-carbon double bond in the product oi the reaction with the phosphorane or the pho~phonate i~ hydrogenatedO
~he hydrogenation may be carried out according to a method known ~E se~ It 1~ pre~erably carried out ln the presence oi a noble ~etal cataly~t, ior example lO~o palladium on carbon, in an inert solvent, ior example methanol or ethyl acetate, at room temperature and under normal preseure.
The llberatlon oi the iunctionally converted hydro2yl group3 to iorm compound~ oi the general iormula I in which OR2 represe~t~ a hydroxyl group may be carried out according to a known methodu For example, an ether protective group is split oii in an aqueou~ ~olutlon o~ an organic acid, ior example acetic acid or propionlc acid, or in an aqueou~ ~olution o~ an inorganic acid, ior example hydrochloric a~id or tetrabutyl ammonium iluoride. In order to improve ~olubility, it 1~
advantageou~ to add an inert, organic ~olvent mi~cible with water.

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S~itable organic sol~ent~ are, ior e~ample, alcohol~, rOr e~am~le methanol and ethanol, and ether~, *or e~ample dimeth~ ogyethane, dioxa~ and tetrahydro~uran. Tetrahydro~ura~ ie pre~erably u~edO
The splitting o~ proce~ pre~erably e~ected at a temperature ~ithln the range o~ ~rom 20C to 80Co The hydroly~is o~ a~ acyl group ls carried out, ~or e~ample, with a~ alkal~ me~al or alkaline earth metal carbonate or hydro~ide in an alcohol or an a~ueou~ solution of an alcoholO
alcohola there come into con~id~ration al~phatic alcohol~, for example methanol, ethanol or butanol, but preierably methanolO
~lk~l~ metal carbonate~ and hydroxides there may be mentioned potassium and sodium carbonates and hydroxides, but potass~um carbonate and potassiu~ hydroxide are pre~erredO ~8 alkaline earth metal carbonate~ and hydroxidea there are ~uitable, ~or example, calc$um carbonate, calcium hydroxide and barium carbonate.
~he reaction takes place at a temperature within the range o~
~rom -10C to 70C, preierablg at 25Co The compounds of the general iormula I are out~tanding3.y ~uitable intermediates ior producing prostaglandin derivative~0 ; ~ccordi~g to~the prostaglandin syntheses hitherto known~
as de~cribed, ior example, ln German Oi~enlegungsschrift No.

2~47,6~0, the production o~ compounds ha~ing unitary ~tereo-chemistry at the C-atom 15 requires estraordinar~ly expensive apparatus and preparati~e separating operations.
~ ccordinglg, there has existed the problem oi developi~g a proce~s or method ior obtaining in a uimple manner auch ¢ompound~
having unitary ~tereochemiatrg a~ the C-atom 150 ~06'~5~
~ he compound~ oi the general ~ormula I are e~pecially e~table fo~ achleving thi~ aimO
The pre~e~t inventio~ accordingl~ ~urther provide3 a proce~
ior the manu~acture oi 13,14-dihydro-15-methyl or -ethyl-P~F2a or a derlvative thereoi, wherein a compound oi the general ior~ula I g~ven above, in which ~, ~ and O~ have the meanings given above, i~ reacted ~Jith a compou~d o~ the ge~eral formu~a V
M-C-C-C$2-CE2~ 3 (V) in ~hioh ~ repreæent~ a metal atom equivalent or a metal-contain~ng group, and the re~ulting compound o~ the general io~mula Vl . i~ ~

~ ~C-C CH ~H ~ (VI) , ~2 OH
~ which B, ~ and OR2 have the meaning~ given above, i~ converted into 1~,14-dih~dro-15-methyl or -ethyl-PG~2~ or a derivative thereoiO
Ths ketone~ oi the general iormula I are easy to prepare by the proces~ oi the present inve~tion and9 aiter reaction with an organo-metal compound o~ the general fo~mula V, can be iurther prooe~sed is a 3imple manner to iorm the kno~n 13,14-dihydro-15-methyl or -ethyl-PGF2 and derivatives thereo~.

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~ he reaction o~ a compound o~ the general ~ormula I with orga~o~metal compol-~d o~ the general ~ormula Y i~ oarried out i.n a manner known ~er ~e in an inert ~olvent or inert ~olvent mi~ture, ior e~ample diethyl ether, tetrahydro~uran~ dioxan or dLimetho~yethane, but pre~erably diethyl ether. The reaction i~
~ected at a temperature within the raDge o~ ~rom 100~ to 60C, and preferably -60C to -30Co The compound o~ the general iormula ~ ~ece~ary ~or ~hi~
reaction i~ prepared by reacti~g the corre~ponding termi~al acetylene-hydrogen compound (M=H) with a~ orga~o-metal compoundO
A~ orga~o-metal compound~ there come into con~ideratio~ lithium butyl, lithium methyl, lithium ethyl, lithium propyl, lithium phenyl, methyl magneeium bromide9 ethyl magne~ium bromide, propyl magne~ium bromldej~butyl magnesium bromide, but preferably litb.ium butyl and methyl magne~ium bromideO
~ he s~mbol M oi the general formula V accordingly prs~erably repre~ent~ an alkali metal atom or an alkali~e earth me~al-halogen groupO ~ advantageously represents a lithium atom or a magnesium-bromine group.
~ he ~pimeric al5 alcohol tPG numbering~ of the general ~ormula VI ~ormed b~ the reaction of the compound of bhe general ~ormula I with the compound o~ the general formula V can be split : up into the two epimers very easily with ~exy good y~eld~ by a method known ~er se, ~or example by ~iltration through ~ilica gel or alumi~ium oxideO

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The compound o~ the general iormula Vl i~ the.~ hydrogenated according to a method known ~ æe in order to convert the carbon-to-carbon triple bond into a carbon-to-carbon single bond and any acyl group i~ de~ired, split o~
According to conventional method~ iree hydroxyl group(~) ~s/are etheri~ied, ior e~ample by *orming a tetrahydropyranyl ethe~, a~d the lactone i8 redueed to the lactol w~th diisobutyl-aluminium hydrideO The lactol is then reacted in a Wittig reaction by a k~own method to iorm the desired pro~taglandin deriYative and, ii de~ired, any protecting group 1~ spl~t o~.
~ he iollowing ~amples illu~trate the invention:-~am~le 1 .

(lS,5R,6R,7R)-6-[(~)-3-O~o-l-butenyl]-7-ben~oylo~y-2-oxabicyclo-C3~,0~octan-3-one . . .
~ o a mixture oi 1046 grams of a ~odium hydride ~uspen~ion (50% ~trength) in mineral oil and 175 ml o~ dimetho~yethane was added dropwise, at 20C under argon, a ~olutio~ Or 5010 grams oi dimethylacetonyl phoephonate in 30 ml oi dimetho%yethane, 1.30 gram~ oi anhydrou~ lithium chloride were added and the whole wa~
etirred ior 2 hours at 20aO ~o thi~ mi~ture ~ae added dropwise a ~olution o~ 8.3 gram~ o~ (lS,5R,6R,7R)-6-~ormy1-7-ben~oyloxy-2-o~abicyclo~3,~,0]octan-3-o~e ~JOAmerOchem.~oc. 96, 5865 (1974)~
in 60 ml oi tetrahydro~ura~ at -10C, and the whole was ~tirred ior 2 hour~ at -10Co ~iter neutralization with glacial acetic acid, ~00 ml of water were added, extraction was carried out three times with 150 ~1 oi a saturated ~olutio~ of ~odium bicar-bonate each tlme and twice with 100 ml oi water each time~

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d~ing was then ¢a~ried out over magne~ium ~lphate and evaporation wa8 e~fected i vacuo. ~ter chromatography o~ the residue over siLlica gel, there were obtained with ether 6.80 grams oi the compound identiiied in the above title a~ colo~rle~ cry~tals, melting at 62 - 6~C.
The phosphonate used to prepare the compound identlfied in the above title wa~ prepared a~ iollow8:
l(a) Dimethylacetonyl phosphonate ~ o a ~olution oi 10906 grams o~ iodoacetone ~n 75 ml o~
benzene were added dropwi~e, at 50 - 55C, 72.1 gram~ of trimethyl pho~phite and the resulting methyl iodide wa~ continuously di~tilled oiiO Heating under reilu~ wa~ then ef~ected for 1 hour and, a~ter di~tillation at 15 torr and 128 - 135C, 55 gram~ o~
dimethylacetonyl pho~phonate were obtained as a colourle~, clear liquid~
Example 2 13,14-Dihydro-15-methyl-proctagland~ n F2a (a) (lS,5R,6R,7R,3lR)-6~ )-3-Hydroxy-3-methyl-oct-1-en-4-yn-l-yl]-7-benzoyloxy-2-oxabicyclo~3,3,0]octan-3-one ~ o a solution of 5.35 gram~ o~ the ketone prepared a~ de~-cribed in E~ample 1 in 160 rl oi ether and 160 ml oi tetrahydroPuran were added dropwise, at -70C under argon, 7806 ml oi a lithlum pentyne ~olution (preparation: to a solution oi 299 gram~ of pentyne-l ~n 57 ~1 o~ tetra`hydro~uran were added dropwise, at -70C under argon, 19.7 ml o~ a 2M lithium butyl solution in hexane and the whole wa~ stirred ~or 10 minute~ at -70C).

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The whol~ was stlrred ~or one hour a~ -70~, 50 ml of a saturated ammonium chloride ~olution were added, the mixture ~a~
al.lowed to warm up to room temperature, e~traction wa~ carried out three times wlth 150 ml o~ ether each time, the organic phase wa~ ~haken twice with 70 ml of water each time, drying was e~ected over magnesium sulphate a~d evaporat~o~ was carried out in vacuo. A~ter chromatography over ~ilica gel (deactivated wi~h

3~ o~ water) there ~ere obtained with pentane/ether (1:1) 1.82 grams o~ the compou~d identi~ied in the above heading (15a-hydroxy) as a colourless oil and, as the more polar component, 1062 grams o~ the 15~-or~entated (according to the PG numbering) compound (lS,5R,6R,7R,3'S)-6-~tE~ hydroxy-3-methyl-oct-1-en-4-yn-1-yl~-7-benzoyloxy-2-oxabicyclo[3,3,0]octan-3-one as a colourless oilO
DC (ether) 15R : R~-ralue 0.28 15S s R~-value 0022 IR o~ the 15R-compound meaæured in chloro~orm solution:
3600, 2960, ~9~5, 2875, 2240, 1770, 1715, 1602, 1585, 1450, 1~70, 973/cmO
(b) (lS,5R,6R,7R,~S)-6-(3-Hydroxy-~-methyl-l-octyl)-7-benzoyloxy-2-o~abicyclo~3~,0]octan-~-one . , . . _ . . _, . , . . , ~
~ solution o~ 1050 gram~ o~ the compound identified in the heading o~ Example 2(a) and prepared as de~cribed in E~ample 2(a) wa~
ln 50 ml of ethyl acetate/shaken, with the addition o~ 60 mg of palladium (lO~o ~trength on carbon), ~or one hour under an atmosphere o~ hydrogen at room tempera~ure~ ~fter iiltering and evaporating the ~olution the residue wa~ chromatographed over .,'~ , .

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si.l~ca gelO With ~ther/hexane (8+2) 1~3 grams oi the compou~d id.enti~ied ~n the abo~e heading were obtained a~ a colourle~3 oil.
DC' (ether) Rf ~alue 0030 ~he ~MR ~pectrum ~howed no ole~inic proton~.
(c) (1~,5R,6R,7R,3~$)-6-(3-Eydroxy-3-methyl-1-octyl) 7-hgdroxy-2-oxabicyclo~3,3,0]octan-3-one To a solution o~ 390 mg o~ the compou~d prepared as de~crlbed in Example 2(b) ln 20 ml o* methanol were adaea. 140 mg o~ anhgdrons pota~ium carbonateg a~d ~he whole was stlrred ~or 2 hours at room temperature under argonO 20 ml o~ OoIN hydrochloric acid were added, and the whole was diluted with 80 ml o~ a saturated ~olution o~ sodium chloride, extracted three time~ with 80 ml o~ ethyl acetate each time, shaken twice with 50 ml of a ~aturated ~olution oi sodium chloride each time, dried over magne~lum sulphate and evaporated in vacuoO The residue waa ~iltered with ether/ethyl acetate (7t3) o~er silica gel, and 260 mg of the compound identi~ied in the above head~ng were obtained as a colourleq~ oilO
W (ether/dioxan 9~1) R~ value 0.25 IR : 3600, 3300, 2995 9 1770/cmO
- (d) (1$,5R,6R~7R,~S)-6-~3-Methyl-3-(tetrahydropyran-~-ylo~y)~
1-o ~1]-7-(tetrahydropyran-2~102y)-2-oxabicyclo[3,3,0]oct~n~
3-one ~ mixture o~ 300 mg o~ the compou~d prepared a~ de~cr~bed in Example 2tc), 105 ml o~ dihydropyran, 3 mg o~ para-toluene sulphonic acid and 15 ml o~ methylene chloride ~Ja~ stirred ~or 20 minutes at , ~

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0C~C, diluted with 80 ml o~ methylene chloride, ~haken in ~ucce~ion wi.th a ~odium bicarbonate solution and a saturated ~olution of ~odium chloride, dried over magne~lum sulphate and eYaporated to dryne~s in vacuo. The residue was iiltered with ether over ~ilica gel and 390 mg o~ the compound identi~ied in the abo~e ~eading were obtained as a colourless oilO
DC (ether) Ri value 0.5~
IR: 2995~ 2960~ 2930~ 1770~ 1120/cmO
(e) (2RS93aR,4R,5R,6aS~3t~)-4-[3-Methyl;3-(tetrahydropyran-2~
ylo~y)-l-octyl]-5-(tetrahydropyran-2-ylo2y)-perhydrocyclo-pentatb~uran-2-ol ~ o a solution, cooled to -60C, oi 360 mg o~ the compound obtained as de~cribed in Example Z(d) in 20 ml o~ toluene were added dropwl~e, under argon, 3 ml o~ a solutlon oi 20~o ~trength o~ diisobutyl aluminium hydrlde in toluene, and the whole wa~
stlrred ~or 30 minutes at -60C, the excsss oi rea~ent uas destroyed by the dropwi~e addition o~ isopropyl ~lcohol, 1051 ml o~ water were added9 the whole wa~ allowed to warm up to room temperature, stirred ~or a ~urther 30 mi~utes, and diluted with 50 ml o~ methylene chloride, and the resulting precipitate was $iltered off. A~ter evaporation, 340 mg Qi the compound identifled in the above heading ~ere obtained a~ a colourle~s oilO
DC (ether) Ri value 0~32 IR: 3600, 3400 (wide), 2985, 2935, 2855/cmO
(~) 13,14-Dihydro-15-methyl-pro~taglandin ~2a-11,15-bis-~tetrahydropyrany13-ether ~ o a ~olution of lo 75 gram~ o~ 4-carbo~ybutyltriphenyl phoæphonium bromide in 8 ml o~ dimethyl ~ulpho~ide (DMS0) were added dropwise at 20~ 709 ml o~ a ~olution o~ methanesulphinyl-Llethyl sodium in DMS0 (preparation: 378 m~ of a ~uspen~ion of 50% strength oi æodium hydride were dissolved in 709 ml o~ DMS0 auring the course of one hour at 75C), and the whole ~a~ stirred ror 20 minute3 at 20C. To this solution were added dropwise 440 mg of the compound prepared as de~cribed in ~xample 2(e), di~#olved in 6 ml oi DMS0, and the whole wa~ ~tirred ~or 2 hours at 48Co 50 ml of ice ~ater were added to the mixture and e~trao-tion waæ e~ected three times with 60 ml o~ ether each timeO
This ether extract was di~cardedO The aqueou~ phase was acidi~ied with an aqueouæ ~olution o~ lO~o strength of citric acid to a pH-value of 5 and extracted four tlmes with 70 ml o~ an ether/
pentane mixture~ each tim~o The organic phase wa~ ~hake~ with 50 ml o~ a saturatea ~olution of ~odium chloride, dried over magne3ium ~ulphate and evapora~ed in vacuo. The re~idue waæ
chromatographed with ether over silioa gel and ~20 mg of the compound identified in the above headirg were obtalned a~ a colourle~æ oilO
Da tchloro~orm/tetrahydro~uran/acetic acid 10/2/1) Ri value 0.51 IR: (chloro~orm): 3600, 3300 (wide), 2990, 2940, 1710 cm.
(g) 13,14-Di~ydro-15-methyl-pro~taglandin F2 100 mg o~ the bi3-(tetrahydropyranyl)-ether obtained a~
described in ~ample 2(i) were ~tirred with 5 ml o~ a ~ixture oi glacial acetic acid/water/tetrahydro~uran (65/~5/10) ~or 4 hour3 I, at 40a, and evaporated to dryness in ~3~ and the re~idue was ~ , . . ." , ~(~69S04 iiltered with methyle~e chloride/i~opropanol (8~2) over silica g~l. 50 sng o~ 13,14-dihydro-15~ethyl-prosta1andi~ F2a were o~tained a~ a colourle~ oilO
W (benzene/dio2an/glaclal acetic acid 20/20/1) R~ ~alue 0028 IX: 3600, 3300 (wide), 3000, 2940, 1705 (wide)/cm.

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Claims (20)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A process for the manufacture of a compound of the general formula (I) (I) in which B represents a -CH2-CH2- or a trans -CH=CH- group, R1 represents a methyl or ethyl group and OR2 represents a hydroxyl group, an acyloxy group or an etherified hydroxyl group, wherein an aldehyde of the general formula (II) (II) in which OR2 represents an acyloxy group or an etherified hydroxyl group, is reacted with a phosphorane of the general formula (III) (III) in which R1 has the meaning given above, or with a phosphonate of the general formula (IV) (IV) in which R1 has the meaning given above, and, when B is required to be a carbon-to-carbon single bond in the compound of formula (I), the carbon-to-carbon trans double bond is hydrogenated ancl when OR2 is required to be a hydroxyl group in the compound of formula (I), the acyloxy group or the etherified hydroxyl group is converted into a free hydroxyl group.

2. A process as claimed in claim 1, wherein the reaction of the aldehyde with the phosphorane is carried out in an inert solvent at a temperature within the range of from 0°C to 100°C.

3. A process as claimed in claim 1, wherein the reaction of the aldehyde with the phosphorane is carried out at 25°C.

4. A process as claimed in claim 1, wherein the reaction of the aldehyde with the phosphonate is carried out in a solvent in the presence of a catalyst at a temperature within the range of from 30°C to -70°C.

5. A process as claimed in claim 4, wherein the catalyst is lithium butyl or sodium hydride.

6. A process as claimed in claim 4 or claim 5, wherein the reaction is carried out at a temperature within the range of from -20°C to 0°C.

7. A process as claimed in claim 1, wherein the hydrogenation is carried out in the presence of a noble metal catalyst.

8. A compound of the formula (I) given in claim 1 when prepared by a process according to claim 1 or an obvious chemical equivalent thereof.

9. A process according to claim 1, wherein in the compound of formula (II) R2 is an acyloxy group, the acyl part of which contains up to 15 carbon atoms and R2 is required to be an acyloxy group in the compound of formula (I).

10. A compound of the formula (I) given in claim 1, wherein R2 represents an acyloxy group, the acyl part of which contains up to 15 carbon atoms, when prepared by a process according to claim 9 or an obvious chemical equivalent thereof.

11. A process according to claim 9, wherein, in the compound of formula (II), R2 is an acetoxy, propionyloxy, butyryloxy, benzoyloxy or paraphenylbenzoyloxy group.

12. A compound of the formula (I) given in claim 1, wherein R2 is an acetoxy, propionyloxy, butyryloxy, benzoyloxy or paraphenylbenzoyloxy group, when prepared by a process according to claim 11 or an obvious chemical equivalent thereof.

13. A process according to claim 1, wherein, in the compound of formula (I), OR2 is required to be an etherified hydroxyl group and in the compound of formula (II), OR2 represents a tetrahydropyranyloxy, tetrahydrofuranyloxy, .alpha.-ethoxyethoxy, trimethylsilyloxy, tri-para-xylyl-silyloxy or dimethyl-tert.-butyl-silyloxy group.

14. A compound of the formula (I) given in claim 1, wherein OR2 is as stated in claim 13, when prepared by a process according to claim 13 or an obvious chemical equivalent thereof.

15. A process according to claim 1, wherein (1S,5R,6R,7R)-6-formyl-7-benzoyloxy-2-oxabicycle[3,3,0]octan-3-one is reacted with dimethylacetonyl phosphonate or triphenyl-acetonyl phosphorane.

16. (1S,5R,6R,7R)-6-[(E)-3-Oxo-1-butenyl]-7-benzoyloxy-2-oxabicyclo[3,3,0]octan-3-one, when prepared by a process according to claim 15 or an obvious chemical equivalent thereof.

17. A process for the manufacture of 13,14-dihydro-15-methyl or -ethyl-PGF2.alpha. or a derivative thereof, wherein a compound of the general formula (I) given in claim 1, in which B, R1 and OR2 have the meanings given in claim 1, is reacted with a compound of the general formula (V) M-C? C-CH2-CH2-CH3 (V), in which M represents a metal atom equivalent or a metal-containing group, and the resulting compound of the general formula (VI) (VI), in which B, R1 and OR2 have the meanings given above, is converted into the required 13,14-dihydro-15-methyl or -ethyl-PGF2.alpha. or the required derivative thereof.

18. A process as claimed in claim 17, wherein M
represents a lithium atom or a magnesium-bromine group.

19. A process as claimed in claim 17, wherein the reaction is carried out in an inert solvent or inert solvent mixture at a temperature within the range of from -100°C to 60°C.

20. A process as claimed in claim 19, wherein the reaction is carried out at a temerature within the range of from -60°C to -30°C.