Methylamine → HCID 58805160, compound

Temperature

0 °C

To a cooled (0° C.), stirred solution of methylamine in dry tetrahydrofuran (1.27 mL of 2.0 M solution; 2.52 mmol) was slowly added a solution of trimethylaluminum in dry toluene (1.27 mL of 2.0 M solution; 2.52 mmol) via syringe under a nitrogen atmosphere. The resulting solution was allowed to warm to room temperature and stir for 2 hours. To the resulting solution, a solution of the 2-hydroxy-4-morpholin-4-yl-benzoic acid methyl ester (100 mg; 0.42 mmol) in dry toluene (4.0 mL) was added via cannula and the resulting solution was heated to reflux for 2 hours. After cooling to room temperature, the reaction was quenched with the careful addition of 1 N aqueous hydrochloric acid to pH 4. The mixture then was extracted with EtOAc (3×10 mL), and the combined organic layers washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was recrystallized from CH2Cl2— hexanes to provide the amide (93 mg; 93%).

1. temperatureto warm to room temperature
2. temperaturethe resulting solution was heated
3. temperatureto reflux for 2 hours
4. temperatureAfter cooling to room temperature
5. customthe reaction was quenched with the careful addition of 1 N aqueous hydrochloric acid to pH 4
6. extractionThe mixture then was extracted with EtOAc (3×10 mL)
7. washthe combined organic layers washed with brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe residue was recrystallized from CH2Cl2— hexanes

ORD record

ord-d0c272842b0448339c748d1436ad6f06

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08242115B2