1-Hydroxybenzotriazole → 1,1-Dimethylethyl 4-[(6-bromo-1,2-benzisoxazol-3-yl)acetyl]-1-piperazinecarboxylate

HRID 1988891Notes

Reaction equation

HRID 1988891 reaction equation
[Br:1][C:2]1[CH:14]=[CH:13][C:5]2[C:6]([CH2:9][C:10]([OH:12])=O)=[N:7][O:8][C:4]=2[CH:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.ON1C2C=CC=CC=2N=N1.[N:49]1([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1>O1CCCC1>[Br:1][C:2]1[CH:14]=[CH:13][C:5]2[C:6]([CH2:9][C:10]([N:52]3[CH2:51][CH2:50][N:49]([C:55]([O:57][C:58]([CH3:61])([CH3:60])[CH3:59])=[O:56])[CH2:54][CH2:53]3)=[O:12])=[N:7][O:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 143452tert-Butyl piperazine-1-carboxylateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 591273762-(6-Bromo-1,2-benzoxazol-3-yl)acetic acid2×

Product 1

HCID 586564751,1-Dimethylethyl 4-[(6-bromo-1,2-benzisoxazol-3-yl)acetyl]-1-piperazinecarboxylateYield 98.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A suspension of (6-bromo-1,2-benzisoxazol-3-yl)acetic acid (Intermediate 32) (0.06 g) and HATU (0.09 g) in dry tetrahydrofuran (2 ml) was stirred at room temp. for 5 min. 1-Hydroxybenzotriazole (0.03 g) and 1,1-dimethylethyl 1-piperazinecarboxylate (0.04 g) were added and the reaction mixture was stirred for a further 18 h. The solvent was removed under vacuum and the residue was partitioned between dichloromethane and 2N aqueous sodium carbonate. The layers were separated and the organic layer was applied to a Varian Bond-Elut SPE cartridge (silica, 5 g ) eluting sequentially with dichloromethane, chloroform, ether and ethyl acetate to give the title compound as a white solid (0.09 g).

Workup

  1. stirringthe reaction mixture was stirred for a further 18 h
  2. customThe solvent was removed under vacuum
  3. customthe residue was partitioned between dichloromethane and 2N aqueous sodium carbonate
  4. customThe layers were separated
  5. washeluting sequentially with dichloromethane, chloroform, ether and ethyl acetate

Sources & evidence

ORD record
ord-d84edfba34144f8c92338cbc8e5bb4b2
Source dataset
uspto-grants-2010_01
Patent number
US07642276B2

Reaction notes

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