Hydrochloric Acid → Tert-butyl 4-[4-(3-methyl-5-{[(2,2,2-trichloroethoxy)carbonyl]amino}isoxazol-4-yl)phenyl]piperazine-1-carboxylate

HRID 1744137Notes

Reaction equation

HRID 1744137 reaction equation
[NH2:1][C:2]1[O:6][N:5]=[C:4]([CH3:7])[C:3]=1[C:8]1[CH:13]=[CH:12][C:11]([N:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)=[CH:10][CH:9]=1.Cl[C:28]([O:30][CH2:31][C:32]([Cl:35])([Cl:34])[Cl:33])=[O:29].CCOCC.Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:7][C:4]1[C:3]([C:8]2[CH:9]=[CH:10][C:11]([N:14]3[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:18][CH2:19]3)=[CH:12][CH:13]=2)=[C:2]([NH:1][C:28]([O:30][CH2:31][C:32]([Cl:35])([Cl:34])[Cl:33])=[O:29])[O:6][N:5]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 870632,2,2-Trichloroethyl chloroformate2×HCID 22236112Tert-butyl 4-[4-(5-amino-3-methylisoxazol-4-yl)phenyl]piperazine-1-carboxylate

Product 1

HCID 22235871Tert-butyl 4-[4-(3-methyl-5-{[(2,2,2-trichloroethoxy)carbonyl]amino}isoxazol-4-yl)phenyl]piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 6344DichloromethaneSolvent

Procedure

To tert-butyl 4-[4-(5-amino-3-methylisoxazol-4-yl)phenyl]piperazine-1-carboxylate (900 mg, 2.51 mmol) and DMAP (1.02 g, 8.3 mmol) in CH2Cl2 (25 mL) at 0° C. under dry nitrogen was added 2,2,2-trichloroethyl chloroformate (1.02 g, 8.3 mmol) dropwise and the reaction was warned to rt and stirred for 1 hour. Additional aliquots of DMAP (1.02 g, 8.3 mmol) and 2,2,2-trichloroethyl chloroformate (1.02 g, 8.3 mmol) were added and the reaction mixture was stirred for 2½ hours. Et2O was added and the reaction was poured into aqueous 10% HCl, extracted with Et2O (2×), dried over Na2SO4, concentrated in vacuo and purified by flash chromatography over silica gel (EtOAc/Hex, 3/7) to afford tert-butyl 4-[4-(3-methyl-5-{[(2,2,2-trichloroethoxy)carbonyl]amino}isoxazol-4-yl)phenyl]piperazine-1-carboxylate.

Workup

  1. customwas warned to rt
  2. stirringthe reaction mixture was stirred for 2½ hours
  3. extractionextracted with Et2O (2×)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. custompurified by flash chromatography over silica gel (EtOAc/Hex, 3/7)

Sources & evidence

ORD record
ord-e45785e241364a6ab37e3ae4e57a256e
Source dataset
uspto-grants-2006_03
Patent number
US07012075B2

Reaction notes

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