N,N-Diethylethanamine trihydrofluoride → rel-(3R,3aR,5R)-5-cyclopropyl-3-(fluoromethyl)-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c][1,2]oxazole

N-(Difluoro-λ4-sulfanylidene)-N-ethylethanaminium tetrafluoroborate (XtalFluor-E, 766 mg, 3.35 mmol) was added to a solution of triethylamine trihydrofluoride (727 μL, 4.46 mmol) in dichloromethane (11 mL). rel-[(3R,3aR,5R)-5-Cyclopropyl-3,3a,4,5-tetrahydro-7H-pyrano[3,4-c][1,2]oxazol-3-yl]methanol (C37) (440 mg, 2.23 mmol) was added, and the reaction mixture was stirred for 2 hours at room temperature. Aqueous sodium bicarbonate solution was added, and the mixture was stirred for 15 minutes, then extracted twice with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 0% to 50% ethyl acetate in heptane) afforded the product as an oil. Yield: 180 mg, 0.904 mmol, 41%. 1H NMR (400 MHz, CDCl3) δ 4.63 (ddd, half of ABX pattern, J=47.4, 10.4, 3.5 Hz, 1H), 4.62 (br d, J=13.3 Hz, 1H), 4.54 (ddd, half of ABX pattern, J=46.7, 10.3, 4.2 Hz, 1H), 4.32 (dddd, J=20.2, 10.3, 3.9, 3.8 Hz, 1H), 4.10 (dd, J=13.4, 1.2 Hz, 1H), 3.28 (br ddd, J=11, 11, 6.5 Hz, 1H), 2.81 (ddd, J=11.0, 7.9, 1.9 Hz, 1H), 2.25 (ddd, J=12.8, 6.5, 1.7 Hz, 1H), 1.61-1.72 (m, 1H), 0.85-0.94 (m, 1H), 0.47-0.59 (m, 2H), 0.34-0.41 (m, 1H), 0.18-0.25 (m, 1H).

1. stirringthe mixture was stirred for 15 minutes
2. extractionextracted twice with dichloromethane
3. dry with materialThe combined organic layers were dried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customPurification via silica gel chromatography (Gradient: 0% to 50% ethyl acetate in heptane)

ORD record

ord-2b652d04595545689dad8f2a4ae3559d

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403846B2