Triethylamine → 3-[Benzyloxy(2,4,6-trimethoxybenzyl)amino]-3-oxopropanoic acid

Temperature

0 °C

To a solution of O-benzyl-N-(2,4,6-trimethoxy-benzyl)hydroxylamine (2.0 g, 6.59 mmol) in dichloromethane (15 mL) was added triethylamine (1.0 mL, 7.25 mmol). The solution was cooled at 0° C. and ethyl malonyl chloride (0.85 mL, 6.59 mmol) was added. Precipitation was gradually formed. The resulting yellow slushy mixture was stirred at 0° C. for 15 min then brought up to rt and stirred for overnight. The solvent was removed under reduced pressure and the crude product was dissolved in EtOAc. The organic solution was consecutively washed with aq. 10% KHSO4 and aq. saturated NaHCO3. The organic layer was dried over Na2SO4 and concentrated. The crude material was stirred in H2O-THF (1:1 by volume, 30 mL) containing NaOH (1.32 g, 33 mmol) for 1 h. The reaction mixture was washed with EtOAc and the aqueous layer was acidified with aq. 10% KHSO4 solution. The product was extracted with EtOAc, dried over Na2SO4, and concentrated to give 1.62 g of 3-[benzyloxy(2,4,6-trimethoxybenzyl)amino]-3-oxopropanoic acid as a white solid (63% yield).

1. customPrecipitation
2. customwas gradually formed
3. customthen brought up to rt
4. stirringstirred for overnight
5. customThe solvent was removed under reduced pressure
6. dissolutionthe crude product was dissolved in EtOAc
7. washThe organic solution was consecutively washed with aq. 10% KHSO4 and aq. saturated NaHCO3
8. dry with materialThe organic layer was dried over Na2SO4
9. concentrationconcentrated
10. stirringThe crude material was stirred in H2O-THF (1:1 by volume, 30 mL)
11. washThe reaction mixture was washed with EtOAc
12. extractionThe product was extracted with EtOAc
13. dry with materialdried over Na2SO4
14. concentrationconcentrated

ORD record

ord-0dbef6d0212e456495110a218a445a0f

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06884907B2