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0 °C

(2R)-2-(tert-Butoxycarbonylamino)-3-(thiophen-2-yl)propionic acid (5.00 g; 18.4 mmol) was dissolved in tetrahydrofuran (60 ml). Methyliodide (9.2 ml; 147 mmol) was added and the solution was cooled to 0° C. Sodiumhydride (60% in oil; 1.90 g; 55.3 mmol) was added in portions and the reaction mixture was stirred at room temperature for two days. Ethyl acetate (50 ml) and water (20 ml) were added dropwise. The solvent was removed in vacuo and the residue was dissolved in ether (30 ml) and water (30 ml). The phases were separated and the organic phase was washed with saturated aqueous sodium hydrogencarbonate (30mi). The aqueous phase were mixed. Citric acid (5% (aq)) was added to pH 3 and the aqueous phase was extracted with ethyl acetate (4×30 ml). The combined organic phases were washed with water (2×30 ml), aqueous sodium thiosulfate (5%; 30 ml), water (30 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The residue was dissolved in ether (10 ml) and dicyclohexylamine (8.5 ml) was added and the mixture was left in a refrigerator overnight. The precipitate was filtered and washed with ether (2×15 ml) and then redissolved in methylene chloride and washed with a mixture of water (15 ml) and sodium hydrogensulfate (15 ml; 10%(aq)). The aqueous phase was washed with methylene chloride (3×15 ml). The combined organic phases were dried over magnesium sulfate and the solvent was removed in vacuo to give 5.10 g of (2R)-2-(N-(tert-Butoxycarbonyl)-N-methylamino)-3-(thiophen-2-yl) propionic acid.

1. customThe solvent was removed in vacuo
2. dissolutionthe residue was dissolved in ether (30 ml)
3. customThe phases were separated
4. washthe organic phase was washed with saturated aqueous sodium hydrogencarbonate (30mi)
5. additionThe aqueous phase were mixed
6. additionCitric acid (5% (aq)) was added to pH 3
7. extractionthe aqueous phase was extracted with ethyl acetate (4×30 ml)
8. washThe combined organic phases were washed with water (2×30 ml), aqueous sodium thiosulfate (5%; 30 ml), water (30 ml)
9. dry with materialdried over magnesium sulfate
10. customThe solvent was removed in vacuo
11. dissolutionThe residue was dissolved in ether (10 ml)
12. additiondicyclohexylamine (8.5 ml) was added
13. waitthe mixture was left in a refrigerator overnight
14. filtrationThe precipitate was filtered
15. washwashed with ether (2×15 ml)
16. dissolutionredissolved in methylene chloride
17. washwashed with a mixture of water (15 ml) and sodium hydrogensulfate (15 ml; 10%(aq))
18. washThe aqueous phase was washed with methylene chloride (3×15 ml)
19. dry with materialThe combined organic phases were dried over magnesium sulfate
20. customthe solvent was removed in vacuo