Carbon Tetrachloride → 1-Benzyloxy-3-chloromethyl-7-fluoro-2-methyl-naphthalene

HRID 1644739Notes

Reaction equation

HRID 1644739 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([Cl:24])(Cl)(Cl)Cl.[CH2:25]([O:32][C:33]1[C:42]2[C:37](=[CH:38][CH:39]=[C:40]([F:43])[CH:41]=2)[CH:36]=[C:35](CO)[C:34]=1[CH3:46])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>O1CCCC1>[CH2:25]([O:32][C:33]1[C:42]2[C:37](=[CH:38][CH:39]=[C:40]([F:43])[CH:41]=2)[CH:36]=[C:35]([CH2:20][Cl:24])[C:34]=1[CH3:46])[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 5943Carbon TetrachlorideHCID 11776TriphenylphosphineHCID 59326595(4-Benzyloxy-6-fluoro-3-methyl-naphthalen-2-yl)-methanol

Product 1

HCID 593265471-Benzyloxy-3-chloromethyl-7-fluoro-2-methyl-naphthaleneYield 77.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A three-neck round-bottom flask was charged with triphenylphosphine (23.33 g, 88.34 mmol), tetrahydrofuran (70 mL), and carbon tetrachloride (35 mL, 0.36 mol) under an argon atmosphere. The resulting mixture was stirred at room temperature for 20 minutes. A solution of (4-benzyloxy-6-fluoro-3-methyl-naphthalen-2-yl)-methanol (13.09 g, 44.17 mmol) in tetrahydrofuran (50 mL) was added rapidly to the reaction mixture via an addition funnel. The reaction mixture was heated at reflux for 1 hour. The reaction mixture was cooled to room temperature, and the solvents were removed in vacuo. The residue was diluted with water, and the resulting mixture was extracted twice with ethyl acetate. The organic phases were washed twice with water, and the resulting aqueous layers were extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over MgSO4, filtered, and concentrated. The crude product was purified using flash chromatography (Analogix SuperFlash™ column, 10-25% dichloromethane in hexane), affording 10.8 g (77%) 1-benzyloxy-3-chloromethyl-7-fluoro-2-methyl-naphthalene as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.02 (dd, J=8.9, 5.9 Hz, 1 H), 7.89 (s, 1 H), 7.53-7.65 (m, 3 H), 7.35-7.50 (m, 4 H), 4.97 (s, 4 H), 2.47 (s, 3 H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 1 hour
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customthe solvents were removed in vacuo
  5. additionThe residue was diluted with water
  6. extractionthe resulting mixture was extracted twice with ethyl acetate
  7. washThe organic phases were washed twice with water
  8. extractionthe resulting aqueous layers were extracted with ethyl acetate
  9. washThe combined organic extracts were washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe crude product was purified

Sources & evidence

ORD record
ord-36b82a52dc7e47e2877bd86c7d9df9cb
Source dataset
uspto-grants-2012_02
Patent number
US08124629B2

Reaction notes

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