Diisopropyl Ether → (R)-4-(4-trifluoromethoxy-benzenesulfonyl)-3-(4-trifluoromethoxy-benzylcarbamoyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 908603Notes

Reaction equation

HRID 908603 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]([O:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=2)(=[O:16])=[O:15])[C@@H:10]([C:28](O)=[O:29])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:31][C:32]([F:43])([F:42])[O:33][C:34]1[CH:41]=[CH:40][C:37]([CH2:38][NH2:39])=[CH:36][CH:35]=1.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.C(OC(C)C)(C)C>CN(C)C=O.CCCCCC>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[CH:18]=[CH:19][C:20]([O:23][C:24]([F:25])([F:27])[F:26])=[CH:21][CH:22]=2)(=[O:16])=[O:15])[C@@H:10]([C:28](=[O:29])[NH:39][CH2:38][C:37]2[CH:40]=[CH:41][C:34]([O:33][C:32]([F:31])([F:42])[F:43])=[CH:35][CH:36]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

8

Reactant 5

HCID 7914Diisopropyl EtherHCID 5718464-(Trifluoromethoxy)benzylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 59703724(R)-4-(4-trifluoromethoxy-benzenesulfonyl)-piperazine-1,3-dicarboxylic acid 1-tert-butyl ester

Product 1

HCID 59703740(R)-4-(4-trifluoromethoxy-benzenesulfonyl)-3-(4-trifluoromethoxy-benzylcarbamoyl)-piperazine-1-carboxylic acid tert-butyl esterYield 66.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8058HexaneSolvent

Procedure

To a solution of the compound (2.40 g) obtained in Step 2, 4-trifluoromethoxybenzylamine (1.21 g) and 1-hydroxybenzotriazole hydrate (1.21 g) in N,N-dimethylformamide (24 ml) was added, with stirring under ice-cooling, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (1.21 g). After stirring overnight at room temperature, and the reaction mixture was partitioned by adding ethyl acetate and water. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution, 10% aqueous citric acid solution and saturated brine, dried over anhydrous magnesium sulfate, filtrated, and concentrated under reduced pressure. The obtained crude crystals were suspended in a mixed solution of diisopropyl ether and n-hexane, collected by filtration and dried to give the title compound (2.20 g).

Workup

  1. temperaturecooling
  2. stirringAfter stirring overnight at room temperature
  3. customthe reaction mixture was partitioned
  4. additionby adding ethyl acetate and water
  5. washThe organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution, 10% aqueous citric acid solution and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltrated
  8. concentrationconcentrated under reduced pressure
  9. customThe obtained crude crystals
  10. filtrationcollected by filtration
  11. customdried

Sources & evidence

ORD record
ord-e56a1777572144d2afa6a197558be3e2
Source dataset
uspto-grants-2011_09
Patent number
US08017612B2

Reaction notes

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