4-Amino-m-cresol → HCID 66746840, compound

Temperature

110 °C

A solution of 4-amino-3-methylphenol (5.45 g, 44.25 mmol) in dry dimethylacetamide (75 mL) was treated with potassium tert-butoxide (10.86 g, 96.77 mmol) and the black mixture was stirred at room temp. until the flask had reached room temp. The contents were then treated with 4-chloro-N-methyl-2-pyridinecarboxamide (Method A2, Step 3b; 7.52 g, 44.2 mmol) and heated at 110° C. for 8 h. The mixture was cooled to room temp. and diluted with water (75 mL). The organic layer was extracted with EtOAc (5×100 mL). The combined organic layers were washed with a saturated NaCl solution (200 mL), dried (MgSO4) and concentrated under reduced pressure. The residual black oil was treated with Et2O (50 mL) and sonicated. The solution was then treated with HCl (1 M in Et2O; 100 mL) and stirred at room temp. for 5 min. The resulting dark pink solid (7.04 g, 24.1 mmol) was removed by filtration from solution and stored under anaerobic conditions at 0° C. prior to use: 1H NMR (DMSO-d6) δ 2.41 (s, 3H), 2.78 (d, J=4.4 Hz, 3H), 4.93 (br s, 2H), 7.19 (dd, J=8.5, 2.6 Hz, 1H), 7.23 (dd, J=5.5, 2.6 Hz, 1H), 7.26 (d, J=2.6 Hz, 1H), 7.55 (d, J=2.6 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 8.55 (d, J=5.9 Hz, 1H), 8.99 (q, J=4.8 Hz, 1H).

1. customhad reached room temp
2. temperatureThe mixture was cooled to room temp.
3. extractionThe organic layer was extracted with EtOAc (5×100 mL)
4. washThe combined organic layers were washed with a saturated NaCl solution (200 mL)
5. dry with materialdried (MgSO4)
6. concentrationconcentrated under reduced pressure
7. additionThe residual black oil was treated with Et2O (50 mL)
8. customsonicated
9. additionThe solution was then treated with HCl (1 M in Et2O; 100 mL)
10. stirringstirred at room temp. for 5 min
11. customstored under anaerobic conditions at 0° C.

ORD record

ord-df9702d26d3d436a913f755e87bfd4fd

Source dataset

uspto-grants-2008_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07351834B1