2-Phenylcyclohexanone oxime synthesis

Yield:22591-17-9 54%

Reaction Conditions:

with hydroxylamine hydrochloride;potassium carbonate in methanol;water-d2 at 20; for 24 h;Inert atmosphere;

Steps:

Synthesis of lactam 12f12

To a solution of 2-phenylcyclohexanone (1.74 g, 10.0 mmol) and hydroxylaminehydrochloride (1.40 g, 17.0 mmol) in MeOH (40 mL) was added K2CO3 (1.52 g in 20 mLof H2O) at room temperature. After stirring for 24 h at room temperature, to the reactionmixture was added H2O at 0 °C, and the precipitate was collected by filtration. The organicsolvent and H2O were removed under reduced pressure to give oxime S5 (1.02 g, 5.40mmol, 54%) as a white solid. To a solution of oxime S5 (300 mg, 1.57 mmol) in pyridine(2.36 mL) was added p-TsCl (172 mg, 1.90 mmol) at room temperature. After stirring for 8h at room temperature, the reaction was quenched with 1 M aqueous HCl. The mixture wasextracted with CH2Cl2 three times, and the combined organic extracts were washed withbrine, dried over anhydrous sodium sulfate, and filtered. The organic solvents wereremoved under reduced pressure to give a crude material, which was purified by silica gelcolumn chromatography (CHCl3-MeOH = 40:1) to afford lactam 12f (236 mg, 1.25 mmol,79%) as a white solid. Rf = 0.50 (Et2O-MeOH = 10:1); mp. 135-137 (CH2Cl2, whiteprisms); IR (neat) 3210, 2921, 2854, 1656, 1445, 1407, 770 cm-1; 1H NMR (400 MHz,CDCl3) δ 7.39-7.27 (m, 5H), 5.68 (br s, 1H), 4.45 (dd, J = 9.6, 4.0 Hz, 1H), 2.63-2.53 (m,2H), 2.10-1.60 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 177.2, 142.4, 129.1, 128.1, 126.2,58.6, 37.12, 37.05, 29.9, 23.1; HRMS (ESI) m/z: calcd. for C12H16NO 190.1226 [M+H+]found 190.1222. Spectroscopic data were identical with those previously reported.13

References:

Itabashi, Suguru;Shimomura, Masashi;Sato, Manabu;Azuma, Hiroki;Okano, Kentaro;Sakata, Juri;Tokuyama, Hidetoshi [Synlett,2018,vol. 29,# 13,p. 1786 - 1790] Location in patent:supporting information