Methyl iodide → (2R)-3-(Benzo[b]thiophen-3-yl)-2-(tert-butoxycarbonyl-methylamino)propionic acid

Temperature

0 °C

(2R)-3-(Benzo[b]thiophen-3-yl)-2-tert-butoxycarbonylamino-propionic acid (2.65 g; 8.25 mmol) was dissolved in dry tetrahydrofuran. Methyl iodide was added and the reaction mixture was cooled to 0° C. Sodium hydride (60% in mineral oil, 0.80 g, 24.8 mmol) was added. The reaction mixture was stirred for 48 hours at room temperature. Ethyl acetate (25 mL) and water (10 mL) were added dropwise. The solvent was removed in vacuo and the residue was dissolved in ether (1 5 mL) and water (15 mL). The organic phase was washed with an aqueous solution of sodium hydrogen carbonate (saturated; 20 mL). To the aqueous phase was added citric acid (5%) until pH 3 and extracted with ethyl acetate (4×20 mL). The combined organic phases were washed with water (2×30 mL), an aqueous solution of sodium thiosulfate (5%; 30 mL) and water (30 mL) and dried (magnesium sulfate). The solvent was removed in vacuo and the residue was dissolved in ether (10 mL). Dicyclohexylamine (5 mL) was added. The precipitated crystals were filtered off, washed with ether (2×10 mL) and dissolved in water (30 mL). An aqueous solution of sodium hydrogen sulfate (10%; 20 mL) and ethyl acetate (40 mL) were added. The aqueous phase was extrated with ethylacetate (4×30 mL) and dried (magnesium sulfate). The solvent was removed in vacuo to afford 3.75 g of (2R)-3-(benzo[b]thiophen-3-yl)-2-(tert-butoxycarbonyl methylamino)propionic acid.

1. customThe solvent was removed in vacuo
2. dissolutionthe residue was dissolved in ether (1 5 mL)
3. washThe organic phase was washed with an aqueous solution of sodium hydrogen carbonate (saturated; 20 mL)
4. additionTo the aqueous phase was added citric acid (5%) until pH 3
5. extractionextracted with ethyl acetate (4×20 mL)
6. washThe combined organic phases were washed with water (2×30 mL)
7. dry with materialan aqueous solution of sodium thiosulfate (5%; 30 mL) and water (30 mL) and dried (magnesium sulfate)
8. customThe solvent was removed in vacuo
9. dissolutionthe residue was dissolved in ether (10 mL)
10. additionDicyclohexylamine (5 mL) was added
11. filtrationThe precipitated crystals were filtered off
12. washwashed with ether (2×10 mL)
13. dissolutiondissolved in water (30 mL)
14. additionAn aqueous solution of sodium hydrogen sulfate (10%; 20 mL) and ethyl acetate (40 mL) were added
15. dry with materialdried (magnesium sulfate)
16. customThe solvent was removed in vacuo

ORD record

ord-acd83277c5424f8992fd0ff45fbaac09

Source dataset

uspto-grants-1999_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05977178