Hydroxyamine hydrochloride → 2-[(1-cyclopropylbut-3-en-1-yl)oxy]-N-hydroxyethanimine

[(1-Cyclopropylbut-3-en-1-yl)oxy]acetaldehyde (C16) (3.63 g from the previous step, ≦13.0 mmol) was dissolved in a 2:1 mixture of ethanol and water (39 mL). Sodium acetate (5.32 g, 64.9 mmol) was added; after the reaction mixture had been stirred for 15 minutes, hydroxylamine hydrochloride (98%, 2.76 g, 38.9 mmol) was added. The reaction mixture was heated to 60° C. for 5 minutes, at which time water (4×1 mL) was added until a solution formed. After 1 hour at 60° C., the reaction mixture was cooled, concentrated under reduced pressure to remove ethanol, and diluted with saturated aqueous sodium chloride solution (100 mL). The mixture was extracted with diethyl ether (3×100 mL), and the combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo at 22° C. Silica gel chromatography (0% to 25% ethyl acetate in heptane) provided the product as a thick, opaque oil. By 1H NMR analysis, this material consisted of a roughly 1:1 mixture of E and Z oxime isomers. Yield: 1.771 g, 10.47 mmol, 81% over two steps. 1H NMR (400 MHz, CDCl3) δ [7.50 (dd, J=5.7, 5.6 Hz) and 6.92-6.99 (m), total 1H], 5.84-5.97 (m, 1H), 5.03-5.15 (m, 2H), {[4.53 (dd, half of ABX pattern, J=16.4, 3.5 Hz) and 4.41 (dd, half of ABX pattern, J=16.4, 3.6 Hz)] and [4.27 (dd, half of ABX pattern, J=12.9, 5.5 Hz) and 4.16 (dd, half of ABX pattern, J=12.9, 5.8 Hz)], total 2H}, 2.65-2.74 (m, 1H), 2.37-2.44 (m, 2H), 0.81-0.91 (m, 1H), 0.59-0.68 (m, 1H), 0.47-0.56 (m, 1H), 0.35-0.44 (m, 1H), 0.07-0.15 (m, 1H).

1. additionwas added until a solution
2. customformed
3. waitAfter 1 hour at 60° C.
4. temperaturethe reaction mixture was cooled
5. concentrationconcentrated under reduced pressure
6. customto remove ethanol
7. additiondiluted with saturated aqueous sodium chloride solution (100 mL)
8. extractionThe mixture was extracted with diethyl ether (3×100 mL)
9. dry with materialthe combined organic layers were dried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo at 22° C
12. customSilica gel chromatography (0% to 25% ethyl acetate in heptane) provided the product as a thick, opaque oil

ORD record

ord-0eb4060a9a6d43f686b160994ff1f7ff

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403846B2