Triethylamine → 2,6-Dimethyl-3-(pivalamidomethyl)benzoic acid

Temperature

0 °C

To a solution of 2,6-dimethyl-3-((2,2,2-trifluoroacetamido)methyl)benzoic acid (3.2 g) in THF (15 mL) was added 1N HCl (15 mL) and the reaction mass was heated at reflux for 3 h. The reaction mixture was concentrated and the crude was co-distilled with toluene to afford 2.0 g of the 3-(aminomethyl)-2,6-dimethylbenzoic acid which was used in the next step without further purification. To a solution of 3-(aminomethyl)-2,6-dimethylbenzoic acid (500 mg, 2.46 mmol) in THF was added N,O-bis(trimethylsilyl)trifluoroacetamide (948 mg, 3.69 mmol) and the reaction mass was heated at reflux for 20 minutes. The reaction mass was cooled to 0° C. and Et3N (1.77 mL, 9.85 mmol) was added, followed by pivaloyl chloride (0.44 mL, 3.69 mmol). The reaction mixture was stirred at rt for 18 h before it was quenched with water and was extracted with chloroform. The organic layer was separated, dried, filtered and concentrated to afford 450 mg of the title product. 1H NMR (300 MHz, DMSO-d6): δ 13.15 (br s, 1H), 7.93 (br t, 1H), 7.08-7.01 (m, 2H), 4.19 (d, J=5.7 Hz, 2H), 2.21 (s, 3H), 2.17 (s, 3H), 1.12 (s, 9H).

1. customwas used in the next step without further purification
2. temperaturethe reaction mass was heated
3. temperatureat reflux for 20 minutes
4. customwas quenched with water
5. extractionwas extracted with chloroform
6. customThe organic layer was separated
7. customdried
8. filtrationfiltered
9. concentrationconcentrated

ORD record

ord-83943a68a7c24fde805d3cb12bb2273a

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09006257B2