Ethyl Bromide → Methyl 4-ethoxy-3-formylbenzoate

HRID 72983Notes

Reaction equation

HRID 72983 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[OH:13])[C:6]([O:8][CH3:9])=[O:7])=[O:2].Br[CH2:15][CH3:16].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(Cl)Cl.CCOCC>[CH2:15]([O:13][C:12]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH:1]=[O:2])[CH3:16]

Participants

7

Reactant 3

HCID 6332Ethyl Bromide2×HCID 11430Potassium CarbonateHCID 212595Benzoic acid, 3-formyl-4-hydroxy-, methyl ester

Product 1

HCID 86672476Methyl 4-ethoxy-3-formylbenzoateYield 101.2%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

A suspension of methyl 3-formyl-4-hydroxy-benzoate (3.0 g, 16.7 mmol), bromoethane (2.7 g, 1.85 mL, 24.9 mmol) and powdered K2CO3 (6.9 g, 49.9 mmol) in DMF (15 mL) was heated at 40° C. for 16 hours. After 16 hours, a further aliquot of bromoethane (1 mL) was added and the reaction mixture was heated for a further 2 hours. The reaction mixture was diluted with DCM (50 mL), filtered and concentrated in vacuo to give a yellow solid, which was diluted with ether (200 mL), washed sequentially with water (50 mL), sat. aq. NaHCO3 (50 mL) and brine solution (50 mL). The organics were separated, dried over MgSO4 and concentrated in vacuo to give methyl 4-ethoxy-3-formylbenzoate (3.52 g, 100%) as a white solid. ESI-MS m/z calc. 208.0. Found 209.3 (M+1)+; Retention time: 1.34 minutes (3 min run). Methyl 4-ethoxy-3-formylbenzoate (1.73 g, 8.91 mmol) was dissolved in THF (20 mL) and cooled to 0° C. LiBH4 (100 mg, 4.59 mmol) was added and the reaction mixture was stirred for 1 hour, then slowly quenched with dropwise addition of acetic acid. The reaction mixture was concentrated in vacuo, diluted with ethyl acetate (50 mL), washed sequentially with sat. aq. NaHCO3 (20 mL) and brine (20 mL). The organics were separated, dried over MgSO4 and purified by silica gel column chromatography using 0-100% EtOAc/DCM as eluent to give methyl 4-ethoxy-3-(hydroxymethyl)benzoate (1.6 g, 46%) as a white solid. ESI-MS m/z calc. 210.0. Found 211.3 (M+1)+; Retention time: 1.11 minutes (3 min run); 1H NMR (400 MHz, CDCl3) δ 8.05-7.86 (m, 2H), 6.99-6.79 (m, 1H), 4.72 (s, 2H), 4.16 (q, J=7.0 Hz, 2H), 3.89 (s, 3H), 1.64 (d, J=7.0 Hz, 2H), 1.47 (t, J=7.0 Hz, 3H).

Workup

  1. temperaturethe reaction mixture was heated for a further 2 hours
  2. filtrationfiltered
  3. concentrationconcentrated in vacuo
  4. customto give a yellow solid, which
  5. washwashed sequentially with water (50 mL), sat. aq. NaHCO3 (50 mL) and brine solution (50 mL)
  6. customThe organics were separated
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-26381676ada94a7d9d2107d612b21c40
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

Loading…