Potassium Hydroxide → Dihexyl ether

A mixture of 0.67 g (120 mmol) of powdered KOH in 20 ml of dry xylene was heated to reflux and ~10 ml of xylene was removed by distillation. To this stirred mixture was added a solution of 400 mg (1.49 mmol) of [1α,2β(Z),3β,4α]-7-[3-(hydroxymethyl)-7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid, methyl ester prepared as described in U.S. Pat. No. 4,143,054 in 6 ml of xylene. Approximately 10 ml of xylene was removed by distillation to afford a clear solution with a gummy precipitate adhering to the magnetic stirring bar. To this mixture was added a solution of 1.45 g (7.5 mmol) of crude 2-methyl-hexylmesylate in 4 ml of xylene. This caused the gummy precipitate to break up to form a somewhat gelatinous reaction mixture. The mixture was refluxed for 21/4 hour. The cooled reaction mixture was partitioned between 20 ml each saturated NH4Cl and EtOAc. The aqueous layer was acidified to pH=3.5 and then extracted with three 20 ml portions of EtOAc. The combined EtOAc extracts were dried (MgSO4), filtered and concentrated in vacuo to give the crude product which was treated with excess ethereal CH2N2. The crude product was purified by flash chromatography on 35 g of silica gel using 4:1 hexane/ether as eluant. Fractions 15-20 were concentrated to give 320 mg of title ether (58%). Fractions 23-27 afforded 100 mg of the n-hexyl ether related to title ether (19%). (Apparently, the commercial 2-methyl-hexanoic acid which was the precursor to the mesylate employed was contaminated with ~10% hexanoic acid) and fractions 21-22 gave 70 mg (13%) of a mixture of these two ethers.

1. temperaturewas heated
2. temperatureto reflux
3. custom~10 ml of xylene was removed by distillation
4. customprepared
5. customApproximately 10 ml of xylene was removed by distillation
6. customto afford a clear solution with a gummy precipitate adhering to the magnetic stirring bar
7. customto form a somewhat gelatinous reaction mixture
8. temperatureThe mixture was refluxed for 21/4 hour
9. customThe cooled reaction mixture
10. customwas partitioned between 20 ml each saturated NH4Cl and EtOAc
11. extractionextracted with three 20 ml portions of EtOAc
12. dry with materialThe combined EtOAc extracts were dried (MgSO4)
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customto give the crude product which
16. additionwas treated with excess ethereal CH2N2
17. customThe crude product was purified by flash chromatography on 35 g of silica gel using 4:1 hexane/ether as eluant
18. concentrationFractions 15-20 were concentrated
19. customto give 320 mg of title ether (58%)

ORDレコード

ord-cf93c171f9b14ae5a00f68c856e94fe4

出典データセット

uspto-grants-1986_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US04582854