Sulfuric Acid → HCID 58129497, compound

Temperature

0 °C

Add 2-(6-trifluoromethyl-pyridin-2-yl)-propan-2-ol (44.4 g, 216 mmol) to acetonitrile (450 mL) and cool the mixture to 0° C. Add concentrated sulfuric acid (35 mL, 657 mmol) and maintain 10° C. or lower during the addition. Warm the mixture to 45° C. for 16.5 hours, then cool the mixture to 4° C. Add 1 N NaOH (1.3 L). Add t-butylmethyl ether (900 mL) and separate the layers. Extract the aqueous layer with t-butylmethyl ether (450 mL) and separate the layers. Combine the organic layers and extract with brine (450 mL), then separate the phases and add anhydrous sodium sulfate. Filter the suspension and concentrate the filtrate to dryness under reduced pressure to afford N-[1-methyl-1-(6-trifluoromethyl-pyridin-2-yl)-ethyl]-acetamide (43.9 g, 219 mmol, 82%). 1H NMR (400 MHz, DMSO d6) δ 8.26 (s, 1H), 7.95 (t, J=7.9 Hz, 1H), 7.63 (dd, J=7.7, 17.4 Hz, 2H), 1.82 (s, 3H), 1.51 (s, 6H). HRMS (ESI) m/z (M+H)1 calcd for C11H14F3N2O (M+H)+: 247.1053, found 247.1051.

1. temperaturemaintain 10° C. or lower during the addition
2. temperatureWarm the mixture to 45° C. for 16.5 hours
3. temperaturecool the mixture to 4° C
4. customAdd t-butylmethyl ether (900 mL) and separate the layers
5. extractionExtract the aqueous layer with t-butylmethyl ether (450 mL)
6. customseparate the layers
7. extractionCombine the organic layers and extract with brine (450 mL)
8. customseparate the phases
9. additionadd anhydrous sodium sulfate
10. filtrationFilter the suspension
11. concentrationconcentrate the filtrate to dryness under reduced pressure

ORD record

ord-d8115395724b4c279562143468a510fc

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426448B2