Acetic Acid → Octahydropentalenol

A stirred solution of 6-[(E)-3-cyclohexyl-(mixture of 3α and 3β)-hydroxyprop-1-enyl]-3-[(E)-4-methoxycarbonylbutylidene]bicyclo[3,3,0]octan-2-one (6.7 mg), prepared as described in Example 8 and predominantly in the 6β-configuration, otherwise known as (±)-methyl(5E,13E)-(9S),[mixture of (15R) and (15S)]-6a-oxo-6,9-methano-15-cyclohexyl-15-hydroxy-16,17,18,19,20-pentanorprosta-5,13-dienoate, in tetrahydrofuran (0.5 ml) at -78° C. was treated dropwise with a solution of lithium tri-sec-butylborohydride in tetrahydrofuran (0.0196 ml; 1.0M). The stirred solution was allowed to warm to 0° during 2 hours and then it was stirred for a further period of 2 hours. Glacial acetic acid (0.15 ml) and water (0.2 ml) were then added to the mixture, which was then concentrated in vacuo. The resulting residue was dissolved in ethyl acetate (10 ml), washed with aqueous sodium bicarbonate solution (2M) and then with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate and concentrated in vacuo. The resulting oil was treated with a solution of sodium hydroxide in 50% v/v aqueous methanol (0.1 ml; 2.5N) and stirred for 150 minutes at 20° C. The mixture was then carefully concentrated in vacuo, and diluted with water (6 ml) and diethyl ether (3 ml). The aqueous phase was separated, acidified to pH 3 by treatment with hydrochloric acid (2N), and extracted with ethyl acetate (4×10 ml). The combined organic extracts were dried over sodium sulphate and concentrated in vacuo. The resulting residue was subjected to chromatography on a silica gel column, using a mixture of ethyl acetate, hexane and glacial acetic acid (50:50:1 by volume) as eluant, to give 3-[(E)-4-carboxybutylidene]-6-[(E)-3-cyclohexyl-(mixture of 3α and 3β)-hydroxyprop-1-enyl]-2-hydroxybicyclo[3,3,0]octane (3.6 mg), predominantly in the 6β,6α-configuration, otherwise known as (±)-(5E,13E)-(6aS,9S),[mixture of (15R) and (15S)]-6a,15-dihydroxy-6,9-methano-15-cyclohexyl-16,17,18,19,20-pentanorprosta-5,13-dienoic acid [NMR in deuterochloroform: multiplets at 5.5, 3.5, 2.7-0.7 p.p.m⟧

1. temperatureto warm to 0° during 2 hours
2. concentrationwas then concentrated in vacuo
3. dissolutionThe resulting residue was dissolved in ethyl acetate (10 ml)
4. washwashed with aqueous sodium bicarbonate solution (2M)
5. dry with materialwith saturated aqueous sodium chloride solution, dried over anhydrous sodium sulphate
6. concentrationconcentrated in vacuo
7. additionThe resulting oil was treated with a solution of sodium hydroxide in 50% v/v aqueous methanol (0.1 ml; 2.5N)
8. stirringstirred for 150 minutes at 20° C
9. concentrationThe mixture was then carefully concentrated in vacuo
10. additiondiluted with water (6 ml) and diethyl ether (3 ml)
11. customThe aqueous phase was separated
12. extractionextracted with ethyl acetate (4×10 ml)
13. dry with materialThe combined organic extracts were dried over sodium sulphate
14. concentrationconcentrated in vacuo
15. additiona mixture of ethyl acetate, hexane and glacial acetic acid (50:50:1 by volume) as eluant

ORDレコード

ord-f127cce32c2a48d3b7f321c1ed6e467b

出典データセット

uspto-grants-1985_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US04517202