Tetrahydrofuran → HCID 86658229, compound

Temperature

0 °C

To a solution of 4-(hydroxymethyl)-N-isopropylcyclohexanecarboxamide (Example 126d, 480 mg, 2.41 mmol) in dry THF (10 mL) was added NaH (60% in mineral oil, 116 mg, 4.82 mmol) in small portions at 0° C. under N2. The reaction mixture was stirred at 0° C. under N2 for 2 h. To this solution was added 2,6-dinitrobenzonitrile (465 mg, 2.41 mmol), and the reaction mixture was stirred at 0° C.—RT for another 2 h, and then at 60° C. overnight under N2 and cooled down to room temperature. The reaction was quenched with brine, and extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was purified by chromatography on silica gel (eluent: 50% EtOAc in hexanes) to give the title compound as yellow solid (594 mg, 71%). 1H NMR (400 MHz, DMSO-d6) δ 1.00 (d,J=7.6 Hz, 6H), 1.22-2.08 (m, 9H), 2.19 (m, 1H), 3.79 (m, 1H), 4.15 (d, J=7.6 Hz, 2H), 7.45 (brs, 1H), 7.78 (d, J=7.2 Hz, 1H), 7.88 (m, 2H). MS 346 (H+).

1. stirringthe reaction mixture was stirred at 0° C.—RT for another 2 h
2. temperatureat 60° C. overnight under N2 and cooled down to room temperature
3. customThe reaction was quenched with brine
4. extractionextracted with EtOAc (3×)
5. washThe combined organic layers were washed with brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. customevaporated under reduced pressure
9. customThe residue was purified by chromatography on silica gel (eluent: 50% EtOAc in hexanes)

ORD record

ord-3815ed0f8a8f4af187be512d58b962a5

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592592B2