1-Hydroxybenzotriazole → (trans)-1-(5-Bromo-benzofuran-2-yl-carbonyl)-4-(4-fluorobenzyl)-2,5-dimethylpiperazine

HRID 1391830Notes

Reaction equation

HRID 1391830 reaction equation
[F:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][N:7]2[CH2:12][C@@H:11]([CH3:13])[NH:10][CH2:9][C@@H:8]2[CH3:14])=[CH:4][CH:3]=1.[Br:17][C:18]1[CH:19]=[CH:20][C:21]2[O:25][C:24]([C:26](O)=[O:27])=[CH:23][C:22]=2[CH:29]=1.ON1C2C=CC=CC=2N=N1.C1(N=C=N)CCCCC1>C(Cl)(Cl)Cl>[Br:17][C:18]1[CH:19]=[CH:20][C:21]2[O:25][C:24]([C:26]([N:10]3[CH2:9][C@@H:8]([CH3:14])[N:7]([CH2:6][C:5]4[CH:15]=[CH:16][C:2]([F:1])=[CH:3][CH:4]=4)[CH2:12][C@@H:11]3[CH3:13])=[O:27])=[CH:23][C:22]=2[CH:29]=1

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 7352475-Bromo-2-benzofurancarboxylic acidHCID 12048208N-CyclohexylcarbodiimideHCID 12112118(2S,5R)-1-(4-Fluorobenzyl)-2,5-dimethylpiperazine

Product 1

HCID 11385259(trans)-1-(5-Bromo-benzofuran-2-yl-carbonyl)-4-(4-fluorobenzyl)-2,5-dimethylpiperazineYield 93%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A mixture of (trans)-1-(4-fluorobenzyl)-2,5-dimethyl-piperazine (220 mg, 1.0 mmol), 5-bromo-1-benzofuran-2-carboxylic acid (342 mg, 1.5 mmol), 1-hydroxybenzotriazol (200 mg, 1.5 mmol) and N-cyclohexylcarbodiimide, N′-methylpolystyrene (167 g, 3.0 mmol of the resin with a loading of 1.8 mmol/g) in CHCl3 was heated under 5 minutes at 110° C. in a microwave oven The mixture was allowed to attain room temperature. TBD-methyl polystyrene (1000 mg, 3 mmol of the resin with a loading of 2.9 mmol/g) was added and the mixture was agitated over night. Both resins were filtered off and washed with CHCl3 and EtOAc. The filtrate was concentrated in vacuo and the residue was submitted to flash column chromatography (toluene→toluene: EtOAc, 20:1→toluene: EtOAc, 1:1) to give the title product in 93% yield.

Workup

  1. customto attain room temperature
  2. additionwas added
  3. filtrationBoth resins were filtered off
  4. washwashed with CHCl3 and EtOAc
  5. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-f7f995d4d8f04a64b2dc00e7ff4740a2
Source dataset
uspto-grants-2008_03
Patent number
US07339059B2

Reaction notes

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