3,5-Dichloro-1-fluoropyridinium triflate → N-(2,6-dichlorobenzoyl)-4-(2,6-dimethoxy-3-fluorophenyl)-L-phenylalanine methyl ester

HRID 1060434Notes

Reaction equation

HRID 1060434 reaction equation
[CH3:1][O:2][C:3](=[O:33])[C@H:4]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:28]([O:29][CH3:30])=[CH:27][CH:26]=[CH:25][C:24]=2[O:31][CH3:32])=[CH:19][CH:18]=1)[NH:5][C:6](=[O:15])[C:7]1[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][C:8]=1[Cl:14].[O-]S([C:38]([F:41])(F)[F:39])(=O)=O.ClC1C=[N+]([F:50])C=C(Cl)C=1>CC#N>[CH3:1][O:2][C:3](=[O:33])[C@H:4]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:24]([O:31][CH3:32])=[CH:25][CH:26]=[C:27]([F:39])[C:28]=2[O:29][CH3:30])=[CH:19][CH:18]=1)[NH:5][C:6](=[O:15])[C:7]1[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][C:8]=1[Cl:14].[CH3:1][O:2][C:3](=[O:33])[C@H:4]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:28]([O:29][CH3:30])=[C:27]([F:50])[CH:26]=[C:38]([F:41])[C:24]=2[O:31][CH3:32])=[CH:19][CH:18]=1)[NH:5][C:6](=[O:15])[C:7]1[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][C:8]=1[Cl:14]

Participants

5

Reactant 2

HCID 27245783,5-Dichloro-1-fluoropyridinium triflate2×HCID 54326841N-(2,6-Dichlorobenzoyl)-4-(2,6-dimethoxyphenyl)-L-phenylalanine methyl ester

Product 2

HCID 53788482N-(2,6-dichlorobenzoyl)-4-(2,6-dimethoxy-3-fluorophenyl)-L-phenylalanine methyl esterHCID 53846883N-(2,6-dichlorobenzoyl)-4-(2,6-dimethoxy-3,5-difluorophenyl)-L-phenylalanine methyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

N-(2,6-Dichlorobenzoyl)-4-(2,6-dimethoxyphenyl)-L-phenylalanine methyl ester (232 mg) was dissolved in anhydrous MeCN (10 mL) under N2 and 3,5-dichloro-1-fluoropyridinium triflate (85%, 353 mg) was added and the mixture was refluxed for 1 day. More 3,5-dichloro-1-fluoropyridinium triflate (175 mg ) was added and the mixture was refluxed for another day. The mixture was then concentrated, and the residue was taken up with water and extracted with CH2Cl2. The extract was washed with sat. NaHCO3, water, dried (MgSO4), filtered and evaporated. The residue was purified by preparative TLC (silica gel; eluent: hexane/AcOEt 5:1 to 2:1) to give N-(2,6-dichlorobenzoyl)-4-(2,6-dimethoxy-3-fluorophenyl)-L-phenylalanine methyl ester(109 mg ) and N-(2,6-dichlorobenzoyl)-4-(2,6-dimethoxy-3,5-difluorophenyl)-L-phenylalanine methyl ester (37 mg).

Workup

  1. temperaturethe mixture was refluxed for 1 day
  2. temperaturethe mixture was refluxed for another day
  3. concentrationThe mixture was then concentrated
  4. extractionextracted with CH2Cl2
  5. washThe extract was washed with sat. NaHCO3, water
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by preparative TLC (silica gel; eluent: hexane/AcOEt 5:1 to 2:1)

Sources & evidence

ORD record
ord-d594336e3e7a40348693981a06bf7d7b
Source dataset
uspto-grants-2003_02
Patent number
US06521666B1

Reaction notes

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