1-Hydroxybenzotriazole → 4-[4-(phenylmethyl)-1-piperazinyl]-N-[(tetrahydro-2H-pyran-2-yl)oxy]-benzamide

HRID 1160153Notes

Reaction equation

HRID 1160153 reaction equation
[C:1]1([CH2:7][N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH:24]1[O:29][NH2:30].ON1C2C=CC=CC=2N=N1>C(Cl)Cl>[C:1]1([CH2:7][N:8]2[CH2:9][CH2:10][N:11]([C:14]3[CH:15]=[CH:16][C:17]([C:18]([NH:30][O:29][CH:24]4[CH2:25][CH2:26][CH2:27][CH2:28][O:23]4)=[O:19])=[CH:21][CH:22]=3)[CH2:12][CH2:13]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 757711-HydroxybenzotriazoleHCID 47417244-(4-benzylpiperazin-1-yl)benzoic AcidHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamine

Product 1

HCID 865980264-[4-(phenylmethyl)-1-piperazinyl]-N-[(tetrahydro-2H-pyran-2-yl)oxy]-benzamideYield 95.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-[4-(phenylmethyl)-1-piperazinyl]-benzoic acid (0.0145 mol), O-(tetrahydro-2H-pyran-2-yl)-hydroxylamine (0.029 mol), N,N-methanetetrayl-biscyclohexanamine (0.0145 mol) and 1-hydroxy-1H-benzotriazole (0.021 mol) in DCM p.a. (200 ml) was stirred at room temperature over the weekend. The reaction mixture was washed with water, dried (MgSO4), filtered and the solvent was evaporated. The residue was crystallized from EtOAc, filtered off and dried, yielding 3.5 g and another crop: 2.0 g total yielding 5.5 g (95%) of 4-[4-(phenylmethyl)-1-piperazinyl]-N-[(tetrahydro-2H-pyran-2-yl)oxy]-benzamide (interm. 8).

Workup

  1. washThe reaction mixture was washed with water
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. customthe solvent was evaporated
  5. customThe residue was crystallized from EtOAc
  6. filtrationfiltered off
  7. customdried
  8. customyielding 3.5 g

Sources & evidence

ORD record
ord-30cdc1a93174478f991ee213a941f18a
Source dataset
uspto-grants-2010_10
Patent number
US07816363B2

Reaction notes

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