Methyl iodide → (2S)-2-(((tert-butoxy)carbonyl)amino)-3-methoxypropanoic acid

A sodium methanolate (NaOMe) solution was prepared by slowly adding MeOH (50 mL) to a suspension of sodium hydride (60% in mineral oil, 28 g, 0.71 mol) in dry THF (1.2 L) at 0° C. The resulting mixture was stirred at RT for 2 h. A portion of the NaOMe solution (320 mL) was added to (S)-2-(tert-butoxycarbonylamino)-3-hydroxypropanoic acid (36 g, 175 mmol) in dry THF (1.6 L), and the mixture was stirred at RT for 1 h. Methyl iodine (16 mL) was then added and the mixture was stirred at RT for 1 h. Another aliquot of NaOMe solution (540 mL) was added and the reaction mixture stirred at RT for 1 h. Additional methyl iodine (38 mL) in THF (200 mL) was added and the reaction mixture was stirred at RT for 36 h. Following reaction, the mixture was concentrated and the residue was dissolved in water and washed with diethyl ether (2×100 mL). The aqueous layer was acidified to pH 2 by the addition of solid citric acid and was extracted with EtOAc (3×200 mL) and dried over Na2SO4. The organic phase was concentrated, and the residue was dissolved in water and extracted with DCM (4×150 mL). The organic layers were combined and concentrated to give the title compound as an oil, which was used without further purification (10.9 g, 28%).

1. stirringthe mixture was stirred at RT for 1 h
2. stirringthe mixture was stirred at RT for 1 h
3. stirringthe reaction mixture stirred at RT for 1 h
4. stirringthe reaction mixture was stirred at RT for 36 h
5. customreaction
6. concentrationthe mixture was concentrated
7. dissolutionthe residue was dissolved in water
8. washwashed with diethyl ether (2×100 mL)
9. additionThe aqueous layer was acidified to pH 2 by the addition of solid citric acid
10. extractionwas extracted with EtOAc (3×200 mL)
11. dry with materialdried over Na2SO4
12. concentrationThe organic phase was concentrated
13. dissolutionthe residue was dissolved in water
14. extractionextracted with DCM (4×150 mL)
15. concentrationconcentrated

ORDレコード

ord-a009339573084f678bf7fde30f03ba50

出典データセット

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09108970B2