Methanol → Methyl 2-bromo-4-methoxybenzoate

HRID 1471348Notes

Reaction equation

HRID 1471348 reaction equation
O=S(Cl)Cl.[Br:5][C:6]1[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[CH:11][C:7]=1[C:8]([OH:10])=[O:9].[CH3:17]O>O>[Br:5][C:6]1[CH:14]=[C:13]([O:15][CH3:16])[CH:12]=[CH:11][C:7]=1[C:8]([O:10][CH3:17])=[O:9]

Participants

5

Reactant 3

HCID 887Methanol2×HCID 24386Thionyl Chloride2×HCID 144847132-Bromo-4-methoxybenzoic acid

Product 1

HCID 15110997Methyl 2-bromo-4-methoxybenzoateYield 85%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
79 °C

Procedure

SOCl2 (7.5 mL, 103.0 mmol) is added dropwise to a stirred 0° C. suspension of 2-bromo-4-methoxybenzoic acid (3) (6.5 g, 28.1 mmol) in methanol (12 mL). The mixture is next stirred at 79° C. for 18 h and then cooled to room temperature before removal of methanol and excess SOCl2 at reduced pressure. The residue is diluted with H2O (50 mL) and extracted with ethyl acetate (100 mL and 70 mL). The extract is washed (2 N NaOH and brine) and dried. After solvent removal at reduced pressure, the residue is purified on silica gel (14.3% to 16.7% ethyl acetate/hexane) to give 5.9 g (85%) of 4 as a colorless liquid. IR 2952, 1728, 1597, 1261 cm−1; 1H NMR (CDCl3) δ 3.83 (s, 3H, CH3O), 3.89 (s, 3H, CO2CH3), 6.86 (dd, J=7.2, 2.0 Hz, 1H, 5-PhH), 7.18 (d, J=2.0 Hz, 1H, 3-PhH), 7.85 ppm (d, J=7.2 Hz, 1H, 6-PhH).

Workup

  1. extractionextracted with ethyl acetate (100 mL and 70 mL)
  2. washThe extract is washed (2 N NaOH and brine)
  3. customdried
  4. customAfter solvent removal at reduced pressure
  5. customthe residue is purified on silica gel (14.3% to 16.7% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-764c725f7f144c22ad483420dd343eec
Source dataset
uspto-grants-2015_04
Patent number
US09012217B2

Reaction notes

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