4-(Trifluoromethoxy)benzylamine → (R)-4-(4-cyclopropyl-benzenesulfonyl)-3-(4-trifluoromethoxy-benzylcarbamoyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 908644Notes

Reaction equation

HRID 908644 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[CH:22]=[CH:21][C:20]([CH:23]3[CH2:25][CH2:24]3)=[CH:19][CH:18]=2)(=[O:16])=[O:15])[C@@H:10]([C:26]([OH:28])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.[F:52][C:53]([F:64])([F:63])[O:54][C:55]1[CH:62]=[CH:61][C:58]([CH2:59][NH2:60])=[CH:57][CH:56]=1>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[CH:22]=[CH:21][C:20]([CH:23]3[CH2:25][CH2:24]3)=[CH:19][CH:18]=2)(=[O:15])=[O:16])[C@@H:10]([C:26](=[O:28])[NH:60][CH2:59][C:58]2[CH:61]=[CH:62][C:55]([O:54][C:53]([F:52])([F:63])[F:64])=[CH:56][CH:57]=2)[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 5718464-(Trifluoromethoxy)benzylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 59703812(R)-4-(4-cyclopropyl-benzenesulfonyl)-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester

Product 1

HCID 59703777(R)-4-(4-cyclopropyl-benzenesulfonyl)-3-(4-trifluoromethoxy-benzylcarbamoyl)-piperazine-1-carboxylic acid tert-butyl esterYield 55.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the compound (168 mg) obtained in Step 2 in N,N-dimethylformamide (1.7 ml) were successively added, with stirring under ice-cooling, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (94 mg), 1-hydroxybenzotriazole hydrate (75 mg) and 4-trifluoromethoxybenzylamine (85 mg). After stirring overnight at room temperature, the mixture was partitioned by adding ethyl acetate, saturated aqueous sodium hydrogen carbonate solution and water. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtrated, and concentrated under reduced pressure. The residue was purified by thin layer silica gel chromatography (hexane:ethyl acetate=1:1) to give the title compound (132 mg).

Workup

  1. temperaturecooling
  2. stirringAfter stirring overnight at room temperature
  3. customthe mixture was partitioned
  4. additionby adding ethyl acetate, saturated aqueous sodium hydrogen carbonate solution and water
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltrated
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by thin layer silica gel chromatography (hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-123ac6dc5e60499ca66f5ab2286c72df
Source dataset
uspto-grants-2011_09
Patent number
US08017612B2

Reaction notes

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