1-(Chloromethoxy)-2-methoxyethane → Methyl 2-(3-bromo-5-formyl-4-((2-methoxyethoxy)methoxy)phenyl)acetate

To a 5-L round-bottom flask was added methyl (3-bromo-5-formyl-4-hydroxy-phenyl)acetate (210 g, 769 mmol, prepared in Reference A above), dichloromethane (2 L), and N,N-diisopropylethylamine (161 mL, 119 g, 923 mmol). A solution of 2-methoxyethoxymethyl chloride (MEM chloride, obtained from TCI America; 106 mL; 923 mmol) in dichloromethane (500 mL) was added dropwise via an addition funnel over 2 h. The reaction was allowed to stir at ambient temperature for overnight, after which time HPLC analysis showed that the reaction was complete. The reaction mixture was diluted with 0.5 N aqueous HCl (1 L) and the solution was allowed to stir at ambient temperature for 0.25 h, then the layers were separated. The organic layer was washed with additional 0.5 N aqueous HCl, followed by saturated aqueous sodium chloride (1 L). The organic layer was concentrated under vacuum to give an oil, which later solidified upon standing. The solid could be crystallized from ethyl acetate and hexane to yield methyl [3-bromo-5-formyl-4-(2-methoxyethoxymethoxy)phenyl]-acetate (237 g) as a colorless solid.

1. stirringto stir at ambient temperature for 0.25 h
2. customthe layers were separated
3. washThe organic layer was washed with additional 0.5 N aqueous HCl
4. concentrationThe organic layer was concentrated under vacuum
5. customto give an oil, which
6. customThe solid could be crystallized from ethyl acetate and hexane

ORD record

ord-9a3321bad9e24b079af4bad88bc9f537

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181280B2