Chloride → HCID 59564617, compound

HRID 2096265Notes

Reaction equation

HRID 2096265 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]([OH:22])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl-].[F:24][C:25]([F:35])([F:34])[C:26]1[CH:27]=[C:28]([NH2:33])[C:29]([NH2:32])=[CH:30][CH:31]=1.C(N(C(C)C)CC)(C)C.[NH4+].[Cl-]>C(Cl)Cl.CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20](=[O:22])[NH:32][C:29]2[CH:30]=[CH:31][C:26]([C:25]([F:24])([F:34])[F:35])=[CH:27][C:28]=2[NH2:33])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

9

Reactant 5

HCID 312ChlorideHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 5208224-Trifluoromethyl-1,2-phenylenediamineHCID 27567762-[4-(tert-Butoxycarbonyl)piperazin-1-yl]benzoic acid

Product 1

HCID 59564617HCID 59564617, compoundYield 49.7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
4 °C

Procedure

4-(2-Carboxy-phenyl)-piperazine-1-carboxylic acid tert-butyl ester, (0.060 g, 0.195 mmol) is dissolved in 5 mL of dry CH2Cl2 under argon. The solution is cooled to 4° C. and a 2 M solution of oxallyl chloride (0.10 mL, 0.21 mmol) is added in a drop-wise fashion resulting in gas evolution. After stirring the mixture for 30 min, 1 drop of DMF is added and the mixture is stirred at room temperature for 30 min. The reaction mixture is cooled to 4° C. and 4-trifluoromethyl-benzene-1,2-diamine (0.069 g, 0.390 mmol) and diisopropylethyl amine (0.092 mL, 0.500 mmol) are added. The reaction is warmed to room temperature and stirred for 1 h. The mixture is diluted with 50 mL EtOAc followed by 20 mL of sat. NH4Cl. The organic phase is washed with 2×20 mL of H2O and 1×20 mL of brine. The organic phase is dried with MgSO4, filtered and concentrated. The residue is applied to a SiO2 prep plate and eluted with 50% EtOAc/hexanes to give 0.045 g of 4-[2-(2-amino-4-trifluoromethyl-phenylcarbamoyl)-phenyl]-piperazine-1-carboxylic acid tert-butyl ester.

Workup

  1. customresulting in gas evolution
  2. stirringthe mixture is stirred at room temperature for 30 min
  3. temperatureThe reaction mixture is cooled to 4° C.
  4. temperatureThe reaction is warmed to room temperature
  5. stirringstirred for 1 h
  6. washThe organic phase is washed with 2×20 mL of H2O and 1×20 mL of brine
  7. dry with materialThe organic phase is dried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. washeluted with 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-5d450b79035f43f3b2f3e596384b847a
Source dataset
uspto-grants-2013_05
Patent number
US08450317B2

Reaction notes

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