Methylamine → N-((1R)-2-(2-Fluorophenyl)-1-(methylcarbamoyl)ethyl)-N-methylcarbamic acid tert-butylester

(2R)-2-(N-tert-Butoxycarbonyl-N-methylamino)-3-(2-fluorophenyl)propionic acid as a dicyclohexylammonium salt (5.57 g; 18.73 mmol) was dissolved in methylene chloride (30 mL) and washed with an aqueous solution of sodium hydrogen sulfate (10%; 30 mL). The organic phase was dried (magnesium sulfate) and filtered. 1-Hydroxybenzotriazole hydrate (2.53 g; 18.73 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (3.75 g; 19.6 mmol) were added to the filtrate and the mixture was stirred for 15 min at room temperature. Methylamine (40% in methanol; 0.53 g; 17.0 mmol) and diisopropylethylamine (3.2 mL; 18.7 mmol) were added and the reaction mixture was stirred for 12 hours at room temperature. The reaction mixture was washed with an aqueous solution of sodium hydrogen carbonate (50 mL) and an aqueous solution of sodium hydrogen sulfate (10%; 50 mL) and dried (magnesium sulfate). The solvent was removed in vacuo and the residue was chromatographed on silica (3.5×40 cm) using ethyl acetate/heptane (2:1) as eluent to afford 2.4 g of N-((1R)-2-(2-Fluorophenyl)-1-(methylcarbamoyl)ethyl)-N-methylcarbamic acid tert-butyl ester.

1. washwashed with an aqueous solution of sodium hydrogen sulfate (10%; 30 mL)
2. dry with materialThe organic phase was dried (magnesium sulfate)
3. filtrationfiltered
4. stirringthe reaction mixture was stirred for 12 hours at room temperature
5. washThe reaction mixture was washed with an aqueous solution of sodium hydrogen carbonate (50 mL)
6. dry with materialan aqueous solution of sodium hydrogen sulfate (10%; 50 mL) and dried (magnesium sulfate)
7. customThe solvent was removed in vacuo
8. customthe residue was chromatographed on silica (3.5×40 cm)

ORD record

ord-6c9ed91ce13341ac93851c1fb33c2bf8

Source dataset

uspto-grants-2003_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06555570B2