Sodium Carbonate → [2-(2,4-Difluoro-phenyl)-6-methoxynaphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone

HRID 1513880Notes

Reaction equation

HRID 1513880 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([C:13](=[O:29])[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)=[CH:16][CH:15]=1)=[C:8](OS(C(F)(F)F)(=O)=O)[CH:7]=[CH:6]2.[F:38][C:39]1[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:40]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(COC)OC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:38][C:39]1[CH:44]=[C:43]([F:45])[CH:42]=[CH:41][C:40]=1[C:8]1[CH:7]=[CH:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=2)[C:9]=1[C:13]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[CH:16][CH:15]=1)=[O:29]

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 27343342,4-Difluorophenylboronic acidHCID 11685250Trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)benzoyl]-naphthalen-2-yl ester

Product 1

HCID 57552512[2-(2,4-Difluoro-phenyl)-6-methoxynaphthalen-1-yl]-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanoneYield 93.6%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

Dissolve trifluoromethanesulfonic acid 6-methoxy-1-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (12.4 g, 23.0 mmol) and 2,4-difluorophenylboronic acid (7.0 g, 46.0 mmol) in degassed dimethoxyethane (620 mL). Add 2M aqueous sodium carbonate (73 mL, 145 mmol) and stir at room temperature under nitrogen for 5 minutes. Add palladium(II) acetate (520 mg, 2.3 mmol) and triphenylphosphine (1.2 g, 4.6 mmol) and plunge into a 85° C. oil bath. Stir for 40 minutes and cool to room temperature. Pour into saturated aqueous sodium bicarbonate and extract twice with methylene chloride. Dry the combined organic layers with sodium sulfate, filter and concentrate in vacuo. Purify the resultant oil with SCX columns (load in methanol, elute with 2M NH3/MeOH) to yield 10.8 g (93%) of the title compound: mass spectrum (ion spray) m/z=502.3 (M+H).

Workup

  1. custominto a 85° C.
  2. stirringStir for 40 minutes
  3. temperaturecool to room temperature
  4. extractionextract twice with methylene chloride
  5. dry with materialDry the combined organic layers with sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customPurify the resultant oil
  9. washwith SCX columns (load in methanol, elute with 2M NH3/MeOH)

Sources & evidence

ORD record
ord-d75380b9c1c64da190118dee07c7176c
Source dataset
uspto-grants-2012_07
Patent number
US08217032B2

Reaction notes

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