Methanol → HCID 86590286, compound

HRID 895345Notes

Reaction equation

HRID 895345 reaction equation
[CH3:1][O:2][C:3](=[O:36])[CH2:4][N:5]1[CH2:10][CH2:9][N:8]([CH:11]([C:29]2[CH:34]=[CH:33][C:32](Br)=[CH:31][CH:30]=2)[CH2:12][O:13][CH2:14][C:15]2[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:17]([C:25]([F:28])([F:27])[F:26])[CH:16]=2)[CH2:7][CH2:6]1.CCN(CC)CC.[CH3:44][OH:45].CN([CH:49]=[O:50])C>>[CH3:44][O:45][C:49](=[O:50])[C:32]1[CH:33]=[CH:34][C:29]([CH:11]([N:8]2[CH2:9][CH2:10][N:5]([CH2:4][C:3]([O:2][CH3:1])=[O:36])[CH2:6][CH2:7]2)[CH2:12][O:13][CH2:14][C:15]2[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[C:17]([C:25]([F:28])([F:27])[F:26])[CH:16]=2)=[CH:30][CH:31]=1

Participants

5

Reactant 4

HCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 86590287HCID 86590287, compound2×

Product 1

HCID 86590286HCID 86590286, compoundYield 30%

Conditions

Temperature
70 °C

Procedure

In a round-bottomed flask fitted with a reflux condenser and a thermometer were introduced {4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-(4-bromo-phenyl)-ethyl]-piperazin-1-yl}-acetic acid methyl ester (compound 184 prepared at example 1.4.1 above; 0.5 g, 0.8 mmoles), Et3N (0.26 ml, 1.8 mmoles), MeOH (3 ml) and DMF (9 ml). The mixture was purged with N2 and a stream of CO was passed into the mixture for 10 min. A solution of Pd(OAc)2 (19.2 mg, 10% moles) and Diphenylphosphinopropane (Dppp) (33 mg, 10% moles) dissolved in MeOH/DMF 1/3 (0.65 ml), purged with N2, was then added to the mixture. The reaction mixture was heated at 70° C. and CO was bubbled through the reaction mixture overnight. The reaction mixture was purged with N2, quenched with NaHCO3 and extracted with AcOEt. The combined organic layers were dried over MgSO4 and concentrated to give an oil which was purified by chromatography on silica gel (eluent: CH2Cl2/MeOH/NH3: 99.5/0.5/0.1 v/v/v) to afford 4-[2-(3,5-Bis-trifluoromethyl-benzyloxy)-1-(4-methoxycarbonylmethyl-piperazin-1-yl)-ethyl]-benzoic acid methyl ester (compound 316; 150 mg, 30%).

Workup

  1. customIn a round-bottomed flask fitted with a reflux condenser
  2. customThe mixture was purged with N2
  3. dissolutionA solution of Pd(OAc)2 (19.2 mg, 10% moles) and Diphenylphosphinopropane (Dppp) (33 mg, 10% moles) dissolved in MeOH/DMF 1/3 (0.65 ml)
  4. custompurged with N2
  5. additionwas then added to the mixture
  6. customCO was bubbled through the reaction mixture overnight
  7. customThe reaction mixture was purged with N2
  8. customquenched with NaHCO3
  9. extractionextracted with AcOEt
  10. dry with materialThe combined organic layers were dried over MgSO4
  11. concentrationconcentrated
  12. customto give an oil which
  13. customwas purified by chromatography on silica gel (eluent: CH2Cl2/MeOH/NH3: 99.5/0.5/0.1 v/v/v)

Sources & evidence

ORD record
ord-5c8604cc22634a05b2961e03c2ab17f7
Source dataset
uspto-grants-2005_07
Patent number
US06916797B2

Reaction notes

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