Hydrochloric Acid → 5-Fluoro-2-(6-hydroxy-2-naphthyl)benzamide

HRID 735373

Reaction equation

HRID 735373 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([OH:12])[CH:6]=[CH:5]2.[F:13][C:14]1[CH:15]=[CH:16][C:17](B2OC(C)(C)C(C)(C)O2)=[C:18]([CH:21]=1)[C:19]#[N:20].C(=O)([O-])[O-:32].[Na+].[Na+].Cl>O1CCOCC1.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>[F:13][C:14]1[CH:15]=[CH:16][C:17]([C:2]2[CH:11]=[CH:10][C:9]3[C:4](=[CH:5][CH:6]=[C:7]([OH:12])[CH:8]=3)[CH:3]=2)=[C:18]([CH:21]=1)[C:19]([NH2:20])=[O:32]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 271446-Bromo-2-naphthalenolHCID 221807905-Fluoro-2-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile

Product 1

HCID 689016405-Fluoro-2-(6-hydroxy-2-naphthyl)benzamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 6-bromo-2-naphthol (12.0 g, 52.2 mmol), 5-fluoro-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzonitrile (16.7 g, 67.6 mmol, prepared according to the method disclosed in patent WO/2003099816), sodium carbonate solution (2M, 75 mL) and tetrakis(triphenylphosphine)palladium (0) (1.2 g, 1.0 mmol) in 1,4-dioxane (360 mL) was heated at 80° C. for 17 hours. It was allowed to cool then poured into dilute hydrochloric acid (1 M, 360 mL) and extracted with ethyl acetate (3×200 mL). These extracts were washed with water and brine then dried (MgSO4), filtered and the solution concentrated in vacuo to a volume of ˜100 mL. Solid was filtered off and sucked dry to give 5-fluoro-2-(6-hydroxy-2-naphthyl)benzamide as a white solid. This solid (6.3 g, 22.4 mmol) was suspended in dichloromethane (130 mL)/pyridine (11 mL) at 0° C. under nitrogen, and trifluoromethane sulfonic anhydride (11 mL, 65.5 mmol) added gradually over 40 minutes before leaving overnight to return to ambient temperature. Solvent was removed in vacuo, water (400 mL) added and extracted into ethyl acetate (2×300 mL). These extracts were washed with water and brine then dried (MgSO4), filtered and solvent removed in vacuo. Purification by flash column chromatography eluting with 10% ethyl acetate/isohexane gave 6-(2-cyano-4-fluorophenyl)-2-naphthyl trifluoromethanesulfonate (8.0 g, 38%). 1H NMR (500 MHz, CDCl3) δ 8.06 (1H, s), 8.01 (2H, dd, J=4.0, 9.0 Hz), 7.82 (1H, d, J=2.3 Hz), 7.73 (1H, dd, J=1.7, 8.5 Hz), 7.60 (1H, dd, J=5.2, 8.6 Hz), 7.53 (1H, dd, J=2.6, 7.9 Hz), 7.47-7.41 (2H, m).

Workup

  1. customprepared
  2. temperatureto cool
  3. extractionextracted with ethyl acetate (3×200 mL)
  4. washThese extracts were washed with water and brine
  5. dry with materialthen dried (MgSO4)
  6. filtrationfiltered
  7. concentrationthe solution concentrated in vacuo to a volume of ˜100 mL
  8. filtrationSolid was filtered off
  9. customsucked dry

Sources & evidence

ORD record
ord-b27f5cf0ae4b43beb311cacc04c5ebbd
Source dataset
uspto-grants-2009_09
Patent number
US07592456B2

Linked notes

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