Water → 4-Methyl-N-(methylsulfonyl)benzamide

To a solution of 4-methylbenzoic acid (1.07 g, 7.82 mmol), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (3.00 g, 15.6 mmol) and N,N-dimethylpyridin-4-amine (2.01 g, 15.6 mmol) in DCM (50 mL) was added methanesulphonamide (1.53 g, 15.6 mmol) and the resulting mixture stirred for 18 hours at room temperature under nitrogen. The reaction mixture was poured into water (100 mL) and extracted with DCM (2×75 mL). The combined organics were dried over magnesium sulphate and evaporated in vacuo, azeotroping with toluene (2×20 mL) to yield a crude solid (2.14 g). The solid was dissolved in DCM (100 mL) and washed with aqueous hydrochloric acid solution (2 M, 2×50 mL). The organic layer was extracted with saturated solution of sodium carbonate (2×50 mL) and the aqueous washed with DCM (50 mL). The basic aqueous layer was acidified to pH 2 with 2 M aqueous hydrochloric acid and extracted with DCM (2×50 mL). The combined organic extracts were washed with water (20 mL), dried over magnesium sulphate and evaporated in vacuo to yield the first crop of the title compound as a white solid (368 mg). All aqueous layers from the extraction process were then evaporated in vacuo to yield a white solid which was triturated with DCM (50 mL). The organics were dried over magnesium sulphate and evaporated in vacuo to yield a white solid, which was redissolved in DCM (50 mL), washed with hydrochloric acid (2 M, 20 mL) dried over magnesium sulphate and evaporated in vacuo to yield a second crop of the title compound as a white crystalline solid (578 mg, combined yield of 56%).

1. extractionextracted with DCM (2×75 mL)
2. dry with materialThe combined organics were dried over magnesium sulphate
3. customevaporated in vacuo
4. customazeotroping with toluene (2×20 mL)
5. customto yield a crude solid (2.14 g)
6. washwashed with aqueous hydrochloric acid solution (2 M, 2×50 mL)
7. extractionThe organic layer was extracted with saturated solution of sodium carbonate (2×50 mL)
8. washthe aqueous washed with DCM (50 mL)
9. extractionextracted with DCM (2×50 mL)
10. washThe combined organic extracts were washed with water (20 mL)
11. dry with materialdried over magnesium sulphate
12. customevaporated in vacuo

ORD record

ord-9c024d3c11da495bb2359dfcc75e1fd7

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09096500B2