Hydrochloric Acid → 6-(4-Fluorophenyl)-2-naphthol

HRID 735302Notes

Reaction equation

HRID 735302 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].Br[C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[CH:14]=[C:13]([OH:18])[CH:12]=[CH:11]2.[F:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1.Cl>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[F:19][C:20]1[CH:25]=[CH:24][C:23]([C:8]2[CH:9]=[C:10]3[C:15](=[CH:16][CH:17]=2)[CH:14]=[C:13]([OH:18])[CH:12]=[CH:11]3)=[CH:22][CH:21]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 271446-Bromo-2-naphthalenolHCID 2856454-Fluorophenylboronic acid

Product 1

HCID 688986336-(4-Fluorophenyl)-2-naphtholYield 74%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Dioxane (100 mL) and 2M sodium carbonate solution (15 mL) were added to a mixture of 6-bromo-2-naphthol (2.3 g, 10 mmol), 4-fluorobenzeneboronic acid (2.2 g, 15 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.6 g). The reaction was heated to 80° C. under nitrogen for 5 hours. The cooled reaction mixture was poured into dilute hydrochloric acid (200 mL) and extracted with ethyl acetate (x3). The combined organic layers were washed with water (x2) and brine, dried over MgSO4 and evaporated in vacuo. The residue was purified by flash column chromatography on silica, eluting with 10-20% ethyl acetate/isohexane, to give 6-(4-fluorophenyl)-2-naphthol as a white solid (1.75 g, 74%). 1H NMR (500 MHz, CDCl3) δ 7.91 (1H, s), 7.80 (1H, d, J=8.8 Hz), 7.75 (1H, d, J=8.5 Hz), 7.65-7.63 (3H, m), 7.18-7.12 (4H, m), 4.97 (1H, s).

Workup

  1. customThe cooled reaction mixture
  2. extractionextracted with ethyl acetate (x3)
  3. washThe combined organic layers were washed with water (x2) and brine
  4. dry with materialdried over MgSO4
  5. customevaporated in vacuo
  6. customThe residue was purified by flash column chromatography on silica
  7. washeluting with 10-20% ethyl acetate/isohexane

Sources & evidence

ORD record
ord-4e374cd588e34be8a92e3da82abb7a4c
Source dataset
uspto-grants-2009_09
Patent number
US07592456B2

Reaction notes

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