1-Hydroxybenzotriazole → Tert-butyl 4-(3-chloro-2-fluorobenzoyl)piperazine-1-carboxylate

HRID 1725502Notes

Reaction equation

HRID 1725502 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[Cl:36][C:37]1[C:38]([F:46])=[C:39]([CH:43]=[CH:44][CH:45]=1)[C:40](O)=[O:41]>C(Cl)(Cl)Cl>[Cl:36][C:37]1[C:38]([F:46])=[C:39]([CH:43]=[CH:44][CH:45]=1)[C:40]([N:11]1[CH2:10][CH2:9][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:13][CH2:12]1)=[O:41]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 143452tert-Butyl piperazine-1-carboxylateHCID 3029313-Chloro-2-fluorobenzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 57562582Tert-butyl 4-(3-chloro-2-fluorobenzoyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

A mixture of 19.4 g of 1-Boc-piperazine, 24.0 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 19.1 g of 1-hydroxybenzotriazole, 20.0 g of 3-chloro-2-fluorobenzoic acid and 200 ml of chloroform was stirred at room temperature for 4 hours. The resulting mixture was diluted with chloroform, and an insoluble matter was filtered off using Celite. Then, the filtrate was washed with water and brine. The resulting organic layer was dried over magnesium sulfate and filtered, and the filtrate was concentrated in vacuo. The resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=9/1 to 1/1) to give title compound.

Workup

  1. filtrationan insoluble matter was filtered off
  2. washThen, the filtrate was washed with water and brine
  3. dry with materialThe resulting organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=9/1 to 1/1)

Sources & evidence

ORD record
ord-bc2e13b43cb148a9a72224b538236cd8
Source dataset
uspto-grants-2009_02
Patent number
US07491720B2

Reaction notes

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