Acetic acid, 2,2-dimethoxy-, methyl ester → N-(5-bromo-2-fluorobenzyl)-2,2-dimethoxyacetamide

HRID 1926248Notes

Reaction equation

Cl.[Br:2][C:3]1[CH:4]=[CH:5][C:6]([F:11])=[C:7]([CH:10]=1)[CH2:8][NH2:9].[CH3:12][O:13][CH:14]([O:19][CH3:20])[C:15](OC)=[O:16].CCN(C(C)C)C(C)C>CO>[Br:2][C:3]1[CH:4]=[CH:5][C:6]([F:11])=[C:7]([CH:10]=1)[CH2:8][NH:9][C:15](=[O:16])[CH:14]([O:19][CH3:20])[O:13][CH3:12]

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 5-bromo-2-fluorobenzylamine hydrochloride (15.0 g, 62 mmol), methyl dimethoxyacetate (10.0 g, 75 mmol), and DIPEA (10.3 mL, 62 mmol) in methanol (15 mL) was heated at 60° C. for 16 h in a bomb apparatus. After cooling to RT, the solvent was evaporated and DCM (150 mL) was added. The solution was washed with water (2×30 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to give the crude product. It was purified by column chromatography on silica gel using EtOAc/Hexanes (1:1) to give the title compound. 1H NMR (CDCl3, 300 MHz) δ=3.42 (s, 6H), 4.53 (d, J=4.8 Hz, 2H), 4.81 (s, 1H), 6.96 (t, J=6.8 Hz, 1H), 7.40-7.42 (m, 1H), 7.51-7.54 (m, 1H). MS(ES+): m/z=305.73/307.69 [MH+]. HPLC: tR=2.89 min (polar—5 min, ZQ2).

Workup

temperatureAfter cooling to RT
customthe solvent was evaporated
additionDCM (150 mL) was added
washThe solution was washed with water (2×30 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customto give the crude product
customIt was purified by column chromatography on silica gel

Sources & evidence

ORD record: ord-557d5c5624f6411a80df14326645f6aa
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08178668B2

Reaction notes

Loading…