Methanol → (4-Benzyloxy-6-fluoro-3-methyl-naphthalen-2-yl)-acetic acid methyl ester

HRID 1644740Notes

Reaction equation

HRID 1644740 reaction equation
[CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([F:19])[CH:17]=2)[CH:12]=[C:11]([CH2:20]Cl)[C:10]=1[CH3:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23](=[O:26])([O-])[O-:24].[K+].[K+].O1CCC[CH2:30]1.CO>O.CCCCCC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C>[CH3:30][O:24][C:23](=[O:26])[CH2:20][C:11]1[C:10]([CH3:22])=[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([F:19])[CH:17]=2)[CH:12]=1

Participants

9

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 593265471-Benzyloxy-3-chloromethyl-7-fluoro-2-methyl-naphthalene

Product 1

HCID 59326535(4-Benzyloxy-6-fluoro-3-methyl-naphthalen-2-yl)-acetic acid methyl ester

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 2 L round bottom flask containing 1-benzyloxy-3-chloromethyl-7-fluoro-2-methyl-naphthalene (10.84 g, 34.44 mmol), PdCl2(PPh3)2 (1.22 g 1.72 mmol, 0.05 eq), and potassium carbonate (5.04 g, 36.50 mmol, 1.06 eq) was evacuated and then backfilled with carbon monoxide gas. A balloon of carbon monoxide was connected into the reaction flask to provide an extra reservoir of CO gas. Tetrahydrofuran (120 mL) was added to the reaction mixture, followed by methanol (58 mL). The reaction mixture was stirred at room temperature for 3 hours, and then diluted with water (600 mL). The resulting mixture was extracted twice with 300 mL portions of ethyl acetate. The combined organic layers were washed with water and brine, dried over MgSO4, filtered, and concentrated to obtain 12.6 g of the crude product. Flash chromatography (Analogix SuperFlash™, 0-15% ethyl acetate in hexane) was used to isolate 11.7 g (quantitative yield) of (4-benzyloxy-6-fluoro-3-methyl-naphthalen-2-yl)-acetic acid methyl ester as a clear, colorless oil that crystallized upon standing at room temperature. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.96 (dd, J=9.1, 5.7 Hz, 1 H), 7.65 (s, 1 H), 7.52-7.62 (m, 3 H), 7.32-7.50 (m, 4 H), 4.94 (s, 2 H), 3.89 (s, 2 H), 3.64 (s, 3 H), 2.31 (s, 3 H).

Workup

  1. customwas evacuated
  2. customto provide an extra reservoir of CO gas
  3. extractionThe resulting mixture was extracted twice with 300 mL portions of ethyl acetate
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto obtain 12.6 g of the crude product

Sources & evidence

ORD record
ord-8bfc801307584d82adce10a44d909476
Source dataset
uspto-grants-2012_02
Patent number
US08124629B2

Reaction notes

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