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

HRID 2363807Notes

Reaction equation

HRID 2363807 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:14]=[C:13]([OH:15])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:16])[CH:11]=2)[CH:6]=1)=[O:4].C([O-])([O-])=O.[K+].[K+].[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(OCC)(=O)C>CN(C=O)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].O>[CH3:1][O:2][C:3]([C:5]1[CH:14]=[C:13]([O:15][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:16])[CH:11]=2)[CH:6]=1)=[O:4]

Participants

8

Reactant 4

HCID 7498Benzyl BromideHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 59326505Methyl 6-fluoro-4-hydroxy-2-naphthoate

Product 1

HCID 593265854-Benzyloxy-6-fluoro-naphthalene-2-carboxylic acid methyl esterYield 88.2%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-fluoro-4-hydroxy-naphthalene-2-carboxylic acid methyl ester (3.7 g, 16.8 mmol) in dry DMF (40 mL) was added K2CO3 (3.25 g, 23.5 mmol), benzyl bromide (3.44 g, 20.2 mmol) and Bu4NI (0.02 g) simultaneously at room temperature under nitrogen. The reaction mixture was stirred for 3 hours at room temperature. The mixture was diluted with water (60 mL) and extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with water (30 mL), brine (30 mL), dried over anhydrous sodium sulfate and concentrated in vacuo to obtain the crude product. Silica gel column chromatography (2%-5% ethyl acetate in hexanes) afforded 4-benzyloxy-6-fluoro-naphthalene-2-carboxylic acid methyl ester (4.6 g, 88%) as an off-white solid. MS cald. for C19H16FO3 [(M+H)+]: 311, obsd. 311.0.

Workup

  1. extractionextracted with ethyl acetate (2×100 mL)
  2. washThe combined organic extracts were washed with water (30 mL), brine (30 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customto obtain the crude product

Sources & evidence

ORD record
ord-7b21e1f395954eefab4b3249891b037f
Source dataset
uspto-grants-2014_04
Patent number
US08691993B2

Reaction notes

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