p-Toluenesulfonic acid → HCID 178506129, compound

HRID 1512168Notes

Reaction equation

HRID 1512168 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[C:25]([F:28])([F:27])[F:26])[CH:5]=[CH:6][C:7]=1[NH:8][C:9](=O)[CH:10]=[CH:11][CH:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1>[O:15]1[CH2:16][CH2:17][CH:12](/[CH:11]=[CH:10]/[C:9]2[NH:8][C:7]3[CH:6]=[CH:5][C:4]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[C:25]([F:28])([F:27])[F:26])=[CH:3][C:2]=3[N:1]=2)[CH2:13][CH2:14]1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 516892Sodium BicarbonateHCID 67527699HCID 67527699, compound

Product 1

HCID 178506129HCID 178506129, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N-(3-amino-2′-trifluoromethyl-biphenyl-4-yl)-3-(tetrahydro-pyran-4-yl)-acrylamide (76.0 mg, 0.195 mmol, as prepared in the previous step) in toluene (5 mL) was treated with p-toluenesulfonic acid (74.2 mg, 0.390 mmol) and heated to 100° C. under a reflux condenser for 4 h. The cooled mixture was treated with saturated aqueous NaHCO3 (50 mL) and extracted with EtOAc (2×50 mL). The combined organic layers were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 24-g Sepra Si 50 SPE column (Isco system: flow rate=20 mL/min; Eluent=1% MeOH—CH2Cl2 for 0-5 min, then 1-4% MeOH—CH2Cl2 for 5-25 min). The resulting residue was purified by RP-HPLC (C18) eluting with CH3CN, 0.1% TFA/water, 10:90 to 50:50, v/v over a period of 20 minutes. The desired column fractions were treated with saturated aqueous NaHCO3 to pH 7 and extracted with EtOAc. The organic layer was dried over MgSO4 and concentrated in vacuo to yield (E)-2-[2-(tetrahydro-pyran-4-yl)-vinyl]-5-(2-trifluoromethyl-phenyl)-1H-benzimidazole as a pale yellow solid.

Workup

  1. extractionextracted with EtOAc (2×50 mL)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified on a 24-g Sepra Si 50 SPE column (Isco system
  5. wait1-4% MeOH—CH2Cl2 for 5-25 min)
  6. customThe resulting residue was purified by RP-HPLC (C18)
  7. washeluting with CH3CN, 0.1% TFA/water, 10:90 to 50:50, v/v over a period of 20 minutes
  8. additionThe desired column fractions were treated with saturated aqueous NaHCO3 to pH 7
  9. extractionextracted with EtOAc
  10. dry with materialThe organic layer was dried over MgSO4
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ca4cbd885fe640409d79800b4d8c2888
Source dataset
uspto-grants-2012_07
Patent number
US08217060B2

Reaction notes

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