Citric Acid → HCID 60197000, compound

HRID 878083Notes

Reaction equation

HRID 878083 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=1.[CH3:14][NH:15][C:16]1[CH:17]=[N:18][CH:19]=[CH:20][C:21]=1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[CH3:28].F[B-](F)(F)F.BrC1C=CC=C[N+]=1CC.CCN(C(C)C)C(C)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl>[CH3:14][N:15]([C:16]1[CH:17]=[N:18][CH:19]=[CH:20][C:21]=1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[CH3:28])[C:7](=[O:9])[C:6]1[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:13])[F:12])=[CH:11][CH:10]=1

Participants

7

Reactant 5

HCID 311Citric AcidHCID 99664-(Trifluoromethyl)benzoic acidHCID 81531DiisopropylethylamineHCID 27363002-Bromo-1-ethylpyridinium tetrafluoroborateHCID 18403336N-methyl-4-o-tolylpyridin-3-amine

Product 1

HCID 60197000HCID 60197000, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-(trifluoromethyl)benzoic acid (115 mg, 605 μmol, CAS RN 328-90-5) in CH2Cl2 (2 mL) were added N-methyl-4-o-tolylpyridin-3-amine (0.1 g, 504 μmol, example 1, intermediate a), 2-bromo-1-ethylpyridinium tetrafluoroborate (166 mg, 605 μmol, CAS RN 878-23-9) and DIPEA (130 mg, 176 μL, 1.01 mmol). The reaction mixture was stirred at room temperature for 66 h. The red solution was poured on 10% aqueous citric acid and dichloromethane and the layers were separated. The aqueous layer was extracted twice with dichloromethane. The combined organic layers were washed with 10% aqueous citric acid solution and brine, dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 20 g column using a MPLC system eluting with EtOAc (isocratic). The compound-containing fractions were evaporated and the residue was dissolved in dichloromethane and the solution washed twice with 2M aqueous Na2CO3 solution, twice with 1M aqueous HCl and once with brine, dried over MgSO4, filtered and evaporated. Brown solid (16%). MS (ESI): m/z=371.14 [M+H]+.

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted twice with dichloromethane
  3. washThe combined organic layers were washed with 10% aqueous citric acid solution and brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. additiontreated with silica gel
  7. customevaporated
  8. customThe compound was purified by silica gel chromatography on a 20 g column
  9. washeluting with EtOAc (isocratic)
  10. customThe compound-containing fractions were evaporated
  11. dissolutionthe residue was dissolved in dichloromethane
  12. washthe solution washed twice with 2M aqueous Na2CO3 solution, twice with 1M aqueous HCl and once with brine
  13. dry with materialdried over MgSO4
  14. filtrationfiltered
  15. customevaporated

Sources & evidence

ORD record
ord-020ea0e8802146ff8bae79515f936bb9
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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