Methylamine → ((1R)-2-(4-fluorophenyl)-1-(methylcarbamoyl)ethyl)-methylcarbamic acid tert-butylester

The dicyclohexylammoniumsalt of (R)-2-(N-tert-butoxycarbonyl-N-methylamino)-3-(4-fluorophenyl)propionic acid (3.00 g; 10.1 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 (1.40 g; 10.1 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (2.0 g; 10.6 mmol) were added to the filtrate and the reaction mixture was stirred for 15 min at room temperature. Methylamine (40% in methanol; 0.75 g; 9.17 mmol) and diisopropylethylamine (1.7 mL; 10.1 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 (sat; 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 (3×40 cm) using ethyl acetate/heptane (2:1) as eluent to afford 1.06 g of ((1R)-2-(4-fluorophenyl)-1-(methylcarbamoyl)ethyl)-methylcarbamic acid tert-butylester.

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 (sat; 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 (3×40 cm)

ORD-Eintrag

ord-08e8f01ae0c14948a48d3044bac42596

Quelldatensatz

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06939880B2