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

HRID 1468327Notes

Reaction equation

HRID 1468327 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:14]([CH3:15])=[C:13]([OH:16])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:17])[CH:11]=2)[CH:6]=1)=[O:4].C([O-])([O-])=O.[K+].[K+].[CH2:24](Br)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN(C=O)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].O>[CH3:1][O:2][C:3]([C:5]1[C:14]([CH3:15])=[C:13]([O:16][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:17])[CH:11]=2)[CH:6]=1)=[O:4]

Participants

7

Reactant 3

HCID 7498Benzyl BromideHCID 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 84.5%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-fluoro-4-hydroxy-3-methyl-naphthalene-2-carboxylic acid methyl ester (21.7 g, 92.7 mmol) in dry DMF (250 mL) was added K2CO3 (17.9 g, 130 mmol), benzyl bromide (13 mL, 111 mmol) and Bu4NI (0.250 g) at room temperature under nitrogen. The reaction mixture was stirred for 3 hours at room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with water, brine, dried over anhydrous sodium sulfate and concentrated to give the crude product, which was purified using silica gel column chromatography (2-5% ethyl acetate-hexane) to yield 4-benzyloxy-6-fluoro-3-methyl-naphthalene-2-carboxylic acid methyl ester (25.4 g, 84%) as an off-white solid. MS calcd. for C20H18FO3 [(M+H)+] 325, obsd. 325.1.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic extracts were washed with water, brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customto give the crude product, which
  6. customwas purified

Sources & evidence

ORD record
ord-038b6819283948beb9acc8ddc80d5a0d
Source dataset
uspto-grants-2015_04
Patent number
US09000044B2

Reaction notes

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