Triethylamine → 3-Cyclohexyl-N-hydroxyprop-2-enamide

to a solution of 3-Cyclohexylacrylic acid (5.30 g, 31.3 mmol) in DMF (100 mL) was added EDC (1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) (7.80 g, 40.7 mmol) and HOBt (1-hydroxybenzotriazole hydrate) (5.07 g, 37.6 mmol). After stirring for 30 min at room temperature hydroxylamine hydrochloride (3.26 g, 47.0 mmol) and triethylamine (6.94 mL, 50.1 mmol) were added. After additional 18 hours stirring at room temperature the precipitate was filtered and washed with DMF. The DMF phases were combined. The solvent was concentrated in vacuo. 1 N HCl (50 mL) was added. After extraction with ethyl acetate (3×100 mL) and dichloromethane (2×100 mL) the organic layers were combined, washed with 1 N HCl (10 mL) and sodium chloride saturated solution (10 mL) and dried with magnesium sulfate. The solvent was removed in vacuo. The product was crystallized from ethyl acetate by addition of petroleum ether. This step removed large amounts of HOBt, the substance was then further purified by preparative HPLC using an acetonitrile/water gradient. This yielded (1.54 g, 9.08 mmol) of 3-Cyclohexyl-N-hydroxy-acrylamide. 1H NMR (300 MHz, [D6-DMSO]: δ=0.99-1.35 (m, 5H) and 1.56-1.73 (m, 5H) (cyclohexyl-CH2), 2.00-2.13 (m, 1H, cyclohexyl CH), 5.67 (d, J=15.7 Hz, 1H, C═C—H), 6.58 (dd, J=15.7 and J=6.3 Hz, 1H, C═C—H), 8.77 (s, 1H) and 10.49 (s, 1H) (NH and OH). 13C NMR (75 MHz, [D6-DMSO]: δ=25.2, 25.5, 31.5 (cyclohexyl-CH2), 41.1Acyclohexyl-CH), 118.8 and 147.1 (C═C), 162.8 (C(═O)NHOH). MS: m/z calcd for (C9H15NO2) [M+H]+ 170; found 170.

1. additionwere added
2. filtrationwas filtered
3. washwashed with DMF
4. concentrationThe solvent was concentrated in vacuo
5. addition1 N HCl (50 mL) was added
6. extractionAfter extraction with ethyl acetate (3×100 mL) and dichloromethane (2×100 mL) the organic layers
7. washwashed with 1 N HCl (10 mL) and sodium chloride saturated solution (10 mL)
8. dry with materialdried with magnesium sulfate
9. customThe solvent was removed in vacuo
10. customThe product was crystallized from ethyl acetate by addition of petroleum ether
11. customThis step removed large amounts of HOBt
12. customthe substance was then further purified by preparative HPLC

ORDレコード

ord-a97351ab34d94f439d8d1e4dfd16ed9e

出典データセット

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08227516B2