Pyridine → rel-(1R,2R)-2-(pent-4-en-1-yl)cyclopropan-1-ol

Temperature

20 °C

A solution (0.45 M) of the preceding compound in hexane was treated with a solution (15%) of Et2Zn (1.2 eq) in toluene, and the resulting solution was cooled in an ice bath. Diiodomethane (1.2 eq) was added dropwise, then the solution was stirred for 1 h before being warmed to 20° C. Pyridine (6 eq) was added, and the slurry was stirred for 15 min then poured onto petroleum ether. The mixture was filtered repeatedly through CELITE until a transparent solution was obtained. This mixture was concentrated at 100 mbar, and the solution that remained (that contained trimethyl{[(trans)-2-pent-4-en-1-ylcyclopropyl]oxy}silane, toluene and pyridine) was further diluted with THF. The mixture was cooled to 0° C. then treated dropwise with a solution (1 M) of TBAF (1.2 eq) in THF. After 10 min, the mixture was allowed to warm to 20° C., and after a further 1 h was poured into H2O. The aqueous phase was extracted with EtOAc, and the combined organic extracts were washed with brine then dried. Removal of the volatiles afforded a residue that was purified by flash chromatography (eluent 0-66% Et2O/petroleum ether) to furnish the title compound (71%) as a colorless liquid. 1H NMR (400 MHz, CDCl3) δ 5.85-5.75 (m, 1H), 5.00 (dd, J=17.1, 1.6 Hz, 1H), 4.94 (br d, J=10.4 Hz, 1H), 3.20 (apparent dt, J=6.4, 2.5 Hz, 1H), 2.10-2.04 (m, 2H), 1.52-1.44 (m, 2H), 1.29-1.19 (m, 1H), 1.15-1.07 (m, 1H), 0.95-0.87 (m, 1H), 0.71-0.66 (m, 1H), 0.31 (apparent q, J=6.0 Hz, 1H).

1. temperaturethe resulting solution was cooled in an ice bath
2. stirringthe slurry was stirred for 15 min
3. additionthen poured onto petroleum ether
4. filtrationThe mixture was filtered repeatedly through CELITE until a transparent solution
5. customwas obtained
6. concentrationThis mixture was concentrated at 100 mbar
7. additionwas further diluted with THF
8. temperatureThe mixture was cooled to 0° C.
9. waitAfter 10 min
10. temperatureto warm to 20° C.
11. extractionThe aqueous phase was extracted with EtOAc
12. washthe combined organic extracts were washed with brine
13. customthen dried
14. customRemoval of the volatiles
15. customafforded a residue that
16. customwas purified by flash chromatography (eluent 0-66% Et2O/petroleum ether)

ORD record

ord-854d5e3176764d8693d506b8e95cc6f8

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08080654B2