Hydrochloric Acid → 2323044-90-0

To a stirred solution of intermediate 158.3 (1.71 g, 11.09 mol) in acetonitrile (13.5 ml) was added 2M HCl (11.09 ml, 22.18 mmol). Stirring was continued for 1.5 h at RT and then carefully basified with 1M NaHCO3. The mixture was extracted with diethyl ether (4×). The organic phases were dried over Na2SO4, filtered and evaporated to dryness to get the crude aldehyde (the NMR showed a mixture of equatorial and axial configuration) witch was dissolved in THF (19 ml) and MeOH (19 ml). To the stirred solution was added DBU (0.092 ml, 0.610 mmol) and stirring was continued for 1 h. The reaction mixture was neutralized with 1M HCl, saturated with NaCl and extracted with EtOAc (6×). The organic phases were dried over Na2SO4, filtered and evaporated to dryness. Purification of the residue by normal phase column chromatography, eluting with a gradient of heptane-EtOAc 80:20 to 0:100, gave the title compound as a colorless oil (1.22 g, 8.70 mmol, 78%): 1H-NMR (600 MHz, DMSO-d6): δ 1.56-2.05 (m, 8H), 2.65 (m, 1H), 4.48 (m, 2H), 9.55 (s, 1H) (equatorial conformation was confirmed by ROESY NMR).

1. extractionThe mixture was extracted with diethyl ether (4×)
2. dry with materialThe organic phases were dried over Na2SO4
3. filtrationfiltered
4. customevaporated to dryness
5. customto get the crude aldehyde (the NMR
6. additiona mixture of equatorial and axial configuration) witch
7. stirringstirring
8. waitwas continued for 1 h
9. extractionextracted with EtOAc (6×)
10. dry with materialThe organic phases were dried over Na2SO4
11. filtrationfiltered
12. customevaporated to dryness
13. customPurification of the residue by normal phase column chromatography
14. washeluting with a gradient of heptane-EtOAc 80:20 to 0:100

ORD record

ord-0a90c4c8e4c64827b1804ced845b3273

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08859535B2