Benzyl Bromide → 4-Benzyloxy-6-fluoro-3-methyl-naphthalene-2-carboxylic acid methyl ester

HRID 1644737Notes

Reaction equation

HRID 1644737 reaction equation
[CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:9][O:10][C:11]([C:13]1[C:22]([CH3:23])=[C:21]([OH:24])[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([F:25])[CH:19]=2)[CH:14]=1)=[O:12].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CC(C)=O>[CH3:9][O:10][C:11]([C:13]1[C:22]([CH3:23])=[C:21]([O:24][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([F:25])[CH:19]=2)[CH:14]=1)=[O:12]

Participants

6

Reactant 4

HCID 7498Benzyl BromideHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 593265736-Fluoro-4-hydroxy-3-methyl-naphthalene-2-carboxylic acid methyl ester

Product 1

HCID 593266024-Benzyloxy-6-fluoro-3-methyl-naphthalene-2-carboxylic acid methyl esterYield 66.2%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Benzyl bromide (10 mL, 82.51 mmol) was added to a mixture of 6-fluoro-4-hydroxy-3-methyl-naphthalene-2-carboxylic acid methyl ester (15.56 g, 66.43 mmol) and potassium carbonate (19.26 g, 136.6 mmol) in acetone (300 mL). The reaction mixture was heated at reflux for 3 hours. The acetone was removed in vacuo. The residue was diluted with water, and the resulting mixture was extracted three times with ethyl acetate. The combined organic phases were washed with brine, dried over MgSO4, filtered, and concentrated. A concentrated solution of the crude product in 25% ethyl acetate in hexanes was loaded onto a Analogix SuperFlash™ column. Flash chromatography (25-50% ethyl acetate in hexanes) provided 14.27 g (66% yield) of 4-benzyloxy-6-fluoro-3-methyl-naphthalene-2-carboxylic acid methyl ester as a slightly yellow solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.34 (s, 1 H), 8.19 (dd, J=8.9, 5.9 Hz, 1 H), 7.64 (dd, J=10.7, 2.3 Hz, 1 H), 7.57 (d, J=6.6 Hz, 2 H), 7.36-7.54 (m, 4 H), 4.98 (s, 2 H), 3.89 (s, 3 H), 2.56 (s, 3 H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 3 hours
  3. customThe acetone was removed in vacuo
  4. additionThe residue was diluted with water
  5. extractionthe resulting mixture was extracted three times with ethyl acetate
  6. washThe combined organic phases were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-e26db155dd34465ba72e58d0a88931ae
Source dataset
uspto-grants-2012_02
Patent number
US08124629B2

Reaction notes

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