Triethylamine → (2'-{[Benzyloxycarbonyl-(2,2,2-trifluoro-ethyl)-amino]-methyl}-6-fluoro-4'-trifluoromethyl-biphenyl-3-yl)-acetic acid methyl ester

HRID 563593Notes

Reaction equation

HRID 563593 reaction equation
[CH3:1][O:2][C:3](=[O:29])[CH2:4][C:5]1[CH:6]=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:13]=2[CH2:22][NH:23][CH2:24][C:25]([F:28])([F:27])[F:26])[C:8]([F:11])=[CH:9][CH:10]=1.Cl[C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32].C(N(CC)CC)C.[H-].[Na+]>C(Cl)Cl.CN(C=O)C.O>[CH3:1][O:2][C:3](=[O:29])[CH2:4][C:5]1[CH:6]=[C:7]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:19])([F:20])[F:21])=[CH:14][C:13]=2[CH2:22][N:23]([C:31]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[O:32])[CH2:24][C:25]([F:28])([F:26])[F:27])[C:8]([F:11])=[CH:9][CH:10]=1

Participants

8

Reactant 4

HCID 8471Triethylamine2×HCID 10387Benzyl chloroformate3×HCID 24758Sodium hydrideHCID 86633170{6-Fluoro-2'-[(2,2,2-trifluoro-ethylamino)-methyl]-4'-trifluoromethyl-biphenyl-3-yl}acetic acid methyl ester

Product 1

HCID 86633173(2'-{[Benzyloxycarbonyl-(2,2,2-trifluoro-ethyl)-amino]-methyl}-6-fluoro-4'-trifluoromethyl-biphenyl-3-yl)-acetic acid methyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

{6-Fluoro-2′-[(2,2,2-trifluoro-ethylamino)-methyl]-4′-trifluoromethyl-biphenyl-3-yl}acetic acid methyl ester (0.26 g, 0.62 mmol), benzyl chloroformate (0.13 mL, 0.93 mmol), and triethylamine (0.13 mL, 0.93 mmol) were combined in CH2Cl2 (2.1 mL), and the reaction was stirred at room temperature for 2 hours. Analytical LCMS indicated that starting material was still present, so additional benzyl chloroformate (0.13 mL, 0.93 mmol), and triethylamine (0.13 mL, 0.93 mmol) were added, and the reaction was stirred for 1 hour. Starting material was still present, so an aqueous work-up was performed, and the residue was dissolved in DMF and cooled to 0° C. Sodium hydride (60% in mineral oil; 0.030 g, 0.75 mmol) was added, followed by benzyl chloroformate (0.13 mL, 0.93 mmol), and the reaction was stirred for 20 minutes. The mixture was worked up with CH2Cl2 and H2O, and the organic layer was dried over MgSO4, filtered, and concentrated. The residue was purified by silica gel chromatography to give the title compound.

Workup

  1. stirringthe reaction was stirred for 1 hour
  2. temperaturecooled to 0° C
  3. stirringthe reaction was stirred for 20 minutes
  4. dry with materialthe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-c5aac1cfb1924448957909d915a0aa61
Source dataset
uspto-grants-2011_11
Patent number
US08067445B2

Reaction notes

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