Hydrochloric Acid → Methyl 2-[(morpholin-4-yl)methyl]benzoate

HRID 1791398Notes

Reaction equation

HRID 1791398 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10]Br.[NH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.Cl>CN(C=O)C>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:10][N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8083MorpholineHCID 2734813Methyl 2-(bromomethyl)benzoate

Product 1

HCID 14857775Methyl 2-[(morpholin-4-yl)methyl]benzoateYield 38.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of N-bromosuccinimide, dibromomethane (3.56 g, 20 mmol) and methyl-2-methylbenzoate (3.04 g, 20 mmol) in 30 mL CHCl3 was refluxed for 4 h. The solvent was evaporated and the residue was purified by column chromatography, with EtOAc:hexanes, 1:5, as eluant, yielding (3.496 g, 76%) of 2-bromomethyl-benzoic acid methyl ester. A solution of 2-bromomethyl-benzoic acid methyl ester (368 mg, 2 mmol) and morpholine (174 mg, 2.0 mmol) in 8 mL DMF with 1 mL HCl (2 N) was refluxed overnight. The solvent was evaporated in vacuo and the residue was purified by column chromatography with EtOAc:hexanes, 1:4, yielding (180 mg, 38%) 2-(morpholin-4-ylmethyl)-benzoic acid methyl ester. The title compound was prepared from 2-(morpholin-4-ylmethyl)-benzoic acid methyl ester, hydrazine and then 3-trifluoromethyl-benzaldehyde in two steps by procedures similar to Example 29. 1H NMR (CDCl3): 8.46 (s, 1H), 8.02 (m, 2H), 7.96 (d, J=7.8 Hz, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.54 (d, J=7.8 Hz, 1H), 7.45 (m, 2H), 7.22 (m, 1H), 3.82 (t, J=4.8 Hz, 4H), 2.64 (t, J=4.8 Hz, 4H).

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue was purified by column chromatography with EtOAc

Sources & evidence

ORD record
ord-61772f1d9878452a9dab16a8c43c752c
Source dataset
uspto-grants-2006_07
Patent number
US07074813B2

Reaction notes

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