Hydrochloric Acid → 2-Amino-3-(benzyloxy)-6-methoxybenzamide

HRID 1519455Notes

Reaction equation

[CH2:1]([O:8][C:9]1[C:10]([N+:20]([O-])=O)=[C:11]([C:15]([O:18][CH3:19])=[CH:16][CH:17]=1)[C:12]([NH2:14])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.O>CCO.[Fe]>[NH2:20][C:10]1[C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:17][CH:16]=[C:15]([O:18][CH3:19])[C:11]=1[C:12]([NH2:14])=[O:13]

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 3-(benzyloxy)-6-methoxy-2-nitrobenzamide (10, 0.34 g. 1.1 mmol), iron powder (0.44 g, 7.7 mmol) and concentrated hydrochloric acid (80 mL) in EtOH (4 mL)/water (0.4 mL) was heated at 90° C. for 75 min. The reaction mixture was cooled to room temperature, filtered through Celite and concentrated. The residue was dissolved in EtOAc washed with saturated NaHCO3 solution, dried over Na2SO4, filtered, and concentrated. Purification by silica gel chromatography eluting with 0-10% MeOH in CH2Cl2 afforded the title compound along with its regioisomer (0.267 g, 87%) as a tan solid: 1H NMR (500 MHz, CDCl3) δ 7.83 (br s, 1H), 7.47-7.32 (m, 5H), 6.77 (d, J=8.8 Hz, 1H), 6.60 (br s, 2H), 6.06 (d, J=8.8 Hz, 1H), 5.51 (br s, 1H), 5.04 (s, 2H), 3.85 (s, 3H).

Workup

temperatureThe reaction mixture was cooled to room temperature
filtrationfiltered through Celite
concentrationconcentrated
dissolutionThe residue was dissolved in EtOAc
washwashed with saturated NaHCO3 solution
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customPurification by silica gel chromatography
washeluting with 0-10% MeOH in CH2Cl2

Sources & evidence

ORD record: ord-f4d5e67783794b838aa409fe13a08174
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09073878B2

Reaction notes

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