Cesium carbonate → HCID 86616678, compound

HRID 1993009Notes

Reaction equation

HRID 1993009 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]([CH3:18])=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([O:19]C)[CH:14]=3)[C:9]=2[OH:21])[CH:5]=[CH:6][CH:7]=1.F[C:23]1[CH:30]=[CH:29][C:26]([CH:27]=[O:28])=[C:25]([C:31]([F:34])([F:33])[F:32])[CH:24]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O.CCOC(C)=O>[OH:19][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[C:9]([O:21][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=[O:28])=[C:25]([C:31]([F:34])([F:33])[F:32])[CH:24]=1)=[C:8]([C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=1)[C:17]([CH3:18])=[CH:16]2

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 5229404-Fluoro-2-(trifluoromethyl)benzaldehydeHCID 68539404HCID 68539404, compound

Product 1

HCID 86616678HCID 86616678, compoundYield 67%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

Compound (283) (1.77 g, 5.43 mmol) was dissolved in HCl (4 N in 1,4-dioxane) (15 mL) and the solution was stirred at RT under N2 for 30 min. The reaction mixture was concentrated to give crude 2-(3-fluorophenyl)-3-methyl-6-(methyloxy)-1-naphthalenol (284) as a gold-yellow oil. 1H NMR (400 MHz, DMSO-d6): δ 2.07 (s, 3H), 3.84 (s, 3H), 6.99-7.44 (m, 6H), 8.04 (d, J=9.3 Hz, 1H), 8.75 (s, 1H). Compound 284 (˜1.50 g, 5.32 mmol) was immediately treated with 4-fluoro-2-trifluoromethylbenzaldehyde (1.53 g, 7.96 mmol) and Cs2CO3 (2.59 g, 7.98 mmol) in DMF (5 mL). The mixture was heated at 110° C. for 16 h, cooled to RT and diluted with 100 mL each H2O and EtOAc. The organic layer was washed with 100 mL each water and brine, dried (Na2SO4) and concentrated to 2.92 g of an amber oil. The oil was purified by column chromatography with 10% EtOAc/hexanes to yield 1.57 g (65%) of the title compound 285 as a white foam. 1H NMR (400 MHz, DMSO-d6): δ 2.20 (s, 3H), 3.88 (s, 3H), 6.96 (dd, J1=2.3 Hz, J2=8.6 Hz, 1H), 7.01-7.14 (m, 4H), 7.17 (d, J=2.5 Hz, 1H), 7.23-7.38 (m, 1H), 7.39 (d, J=2.5 Hz, 1H), 7.93 (d, J=9.1 Hz, 1H), 7.79 (s, 1H), 7.90 (d, J=8.7 Hz, 1H), 10.02 (s, 1H).

Workup

  1. temperaturecooled to RT
  2. washThe organic layer was washed with 100 mL each water and brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated to 2.92 g of an amber oil
  5. customThe oil was purified by column chromatography with 10% EtOAc/hexanes

Sources & evidence

ORD record
ord-9683aa59c34643879c9fbd6654b60a4e
Source dataset
uspto-grants-2010_01
Patent number
US07649093B2

Reaction notes

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