Butyl iodide → HCID 89886634, compound

Temperature

0 °C

To a solution of (2S,3S,4S)-4-(benzyloxy)-2-methyl-3,4-dihydro-2H-pyran-3-ol (0.100 g, 0.454 mmol) in DMF (2.67 ml) at 0° C. was added NaH (45.0 mg, 1.13 mmol, 60% dispersion in mineral oil) and the reaction was stirred for 20 min at 0° C. Tetrabutylammonium iodide (34.0 mg, 0.091 mmol) and 1-iodobutane (0.20 mL, 1.76 mmol) were added and the reaction was stirred at room temperature for 18 h. The reaction was cooled to 0° C., additional NaH in (23.0 mg, 0.575 mmol) and 1-iodobutane (0.10 mL, 0.879 mmol) were added, and the reaction was warmed to 70° C. and stirred for 4 h. The reaction was cooled to room temperature, quenched with H2O, and extracted with EtOAc. The organic layer was separated and the aqueous layer was further extracted with EtOAc. The combined organic phases were washed with brine, dried over MgSO4, filtered, and concentrated to yield a pale-yellow oil. Purification of the crude oil by flash chromatography (SiO2, hexanes/EtOAc gradient) yielded the title compound as a colorless oil (93.0 mg, 74%): IR (neat) 2933, 2871, 1646, 1453, 1239, 1107, 1056, 734, 697 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.41-7.24 (m, 5H), 6.34 (dd, J=6.1, 1.3 Hz, 1H), 4.83 (dd, J=6.1, 2.5 Hz, 1H), 4.67 (d, J=11.7 Hz, 1H), 4.59 (d, J=11.7 Hz, 1H), 4.11 (ddd, J=6.5, 2.2, 1.6 Hz, 1H), 3.89 (ddd, J=13.5, 9.3, 6.7 Hz, 1H), 3.83 (dt, J=9.2, 6.5 Hz, 1H), 3.63 (dt, J=9.2, 6.6 Hz, 1H), 3.30 (dd, J=9.0, 6.6 Hz, 1H), 1.64-1.51 (m, 2H), 1.44-1.33 (m, 2H), 1.38 (d, J=6.4 Hz, 3H), 0.92 (t, J=7.4 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 144.82, 138.69, 128.49, 127.81, 127.69, 100.49, 80.35, 76.53, 74.29, 72.32, 70.83, 32.52, 19.47, 17.53, 14.06; HRMS-ESI (m/z) [M]+ calcd for C17H24O3, 276.1725; found, 276.1710.

1. stirringthe reaction was stirred at room temperature for 18 h
2. temperatureThe reaction was cooled to 0° C.
3. temperaturethe reaction was warmed to 70° C.
4. stirringstirred for 4 h
5. temperatureThe reaction was cooled to room temperature
6. customquenched with H2O
7. extractionextracted with EtOAc
8. customThe organic layer was separated
9. extractionthe aqueous layer was further extracted with EtOAc
10. washThe combined organic phases were washed with brine
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated
14. customto yield a pale-yellow oil
15. customPurification of the crude oil by flash chromatography (SiO2, hexanes/EtOAc gradient)

ORD record

ord-6dc58eb9221744cfa1edb5284b57a2ba

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08785479B2