Acetic Acid → HCID 178480581, compound

Temperature

125 °C

A mixture of trans-N-(2,2-Dimethoxyethyl)-4-hydroxy-N-methylcyclohexanecarboxamide (265 mg, 1.08 mmol) and Ammonium acetate (2.2 g, 29 mmol) in AcOH (3.0 mL, 53 mmol) was heated to reflux (oil bath temperature 125° C.) for 16.5 h. To the cooled solution were added 10 N NaOH (≈10 mL) and water (≈10 mL), and the mixture was extracted with DCM (3×20 mL). The combined DCM extracts were washed with brine, dried over MgSO4, filtered, and concentrated to give the title compound as light orange solid. Additional material was obtained by saturating the aqueous layer from the previous extractions with NaCl and extracting with more DCM (4×25 mL). The light orange solid was chromatographed on silica gel [Isco Combiflash, 2.5 g loading column/4 g Gold column, eluting with DCM→10% 7N NH3 in MeOH] to give the title compound as yellow solid. 1H NMR (400 MHz, CDCl3): δ=6.92 (d, J=1.4 Hz, 1H), 6.77 (d, J=1.4 Hz, 1H), 3.73 (tt, J=10.8, 4.2 Hz, 1H), 3.60 (s, 3H), 2.60 (tt, J=12.0, 3.6 Hz, 1H), 2.18-2.08 (m, 2H), 1.99-1.91 (m, 2H), 1.88 (brs, 1H), 1.83-1.71 (m, 2H), 1.46-1.35 (m, 2H). MS (ES+): m/z=181.13 (100) [MH+]. HPLC: tR=0.69 min (very polar—5 min, ZQ3). UV: λmax=216 nm.

1. temperaturewas heated
2. extractionthe mixture was extracted with DCM (3×20 mL)
3. washThe combined DCM extracts were washed with brine
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated

ORD record

ord-a9dbbdaab9344aa4ac16145b21d67bae

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08445510B2