Trifluoromethanesulfonic anhydride → 1,1-Dimethylethyl 4-(6-bromo-1,2-benzisoxazol-3-yl)-1-piperazinecarboxylate

HRID 1988885Notes

Reaction equation

HRID 1988885 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][C:5]2[C:6](=O)[NH:7][O:8][C:4]=2[CH:3]=1.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.[N:27]1([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.C(N(C(C)C)CC)(C)C>ClCCl.C1CCCCC1.C(#N)C.N1C=CC=CC=1>[Br:1][C:2]1[CH:11]=[CH:10][C:5]2[C:6]([N:30]3[CH2:29][CH2:28][N:27]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:32][CH2:31]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

9

Reactant 4

HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 112296276-bromo-1,2-benzisoxazol-3-ol2×

Product 1

HCID 586564881,1-Dimethylethyl 4-(6-bromo-1,2-benzisoxazol-3-yl)-1-piperazinecarboxylateYield 19.5%

Reagents, catalysts & solvents 4

HCID 1049PyridineSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8078CyclohexaneSolvent

Procedure

An ice-bath cooled solution of 6-bromo-1,2-benzisoxazol-3 (2H)-one (Intermediate 24) (0.05 g) and dry pyridine (0.05 ml) in dry dichloromethane (4 ml) was stirred under nitrogen and treated with triflic anhydride (60 μL). The solution was stirred at room temp. for 4 h, diluted with cyclohexane then applied to a Varian Bond-Elut SPE cartridge (silica, 1 g) and eluted with dichloromethane to give a yellow oil. The oil was dissolved in acetonitrile (2 ml) treated with 1,1-dimethylethyl 1-piperazinecarboxylate (0.04 g) and diisopropylethylamine (0.05 ml) then stirred at 70° under nitrogen for 20 h. The cooled reaction mixture was purified on a Varian Bond-Elut SPE cartridge (silica, 5 g) using dichloromethane:methanol to give the title compound as a white solid (0.016 g).

Workup

  1. stirringThe solution was stirred at room temp. for 4 h
  2. washeluted with dichloromethane
  3. customto give a yellow oil
  4. stirringthen stirred at 70° under nitrogen for 20 h
  5. customThe cooled reaction mixture
  6. customwas purified on a Varian Bond-Elut SPE cartridge (silica, 5 g)

Sources & evidence

ORD record
ord-c336b2c948e247f388a9f28063766767
Source dataset
uspto-grants-2010_01
Patent number
US07642276B2

Reaction notes

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