1-Hydroxybenzotriazole → Methyl 3-(4-isobutyrylpiperazine-1-carbonyl)benzoate

HRID 415311

Reaction equation

HRID 415311 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][CH:13]=1)[C:8]([OH:10])=O)=[O:4].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[CH3:36][CH:37]([CH3:46])[C:38]([N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1)=[O:39]>ClCCl.O.C(N(CC)CC)C>[C:38]([N:40]1[CH2:45][CH2:44][N:43]([C:8]([C:7]2[CH:6]=[C:5]([CH:13]=[CH:12][CH:11]=2)[C:3]([O:2][CH3:1])=[O:4])=[O:10])[CH2:42][CH2:41]1)(=[O:39])[CH:37]([CH3:46])[CH3:36]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 6018803-(Methoxycarbonyl)benzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27614092-Methyl-1-(piperazin-1-yl)propan-1-one

Product 1

HCID 66621314Methyl 3-(4-isobutyrylpiperazine-1-carbonyl)benzoateYield 94%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 3-(methoxycarbonyl)benzoic acid (0.9 g, 5 mmol) in dichloromethane (20 mL), 1-hydroxybenzotriazole (0.75 g, 5.5 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.06 g, 5.5 mmol) and triethyl amine (2 mL) was added. The mixture was stirred at room temperature for 30 min, then 2-methyl-1-(piperazin-1-yl)propan-1-one (1.0 g, 5 mmol) was added and the mixture was stirred at room temperature for 16 h. The resulting mixture was added water (50 mL) and extracted with dichloromethane (100 mL×3). The organic phase was washed with sodium bicarbonate and brine and concentrated. The crude product was purified by column chromatography (silica gel, petroleum ether/ethyl acetate 20:1 to 2:1) to give 1.25 g of methyl 3-(4-isobutyrylpiperazine-1-carbonyl)benzoate as an oil. Yield 94%. 1H-NMR (400 MHz, CDCl3) 1.14-1.15 (d, J=6.4 Hz, 6H), 2.81 (brs, 1H), 3.44-3.80 (m, 8H), 3.94 (s, 3H), 7.52-7.55 (t, J=7.6 Hz, 1H), 7.62-7.64 (d, J=8.0 Hz, 1H), 8.08-8.14 (m, 2H); LC-MS (ESI) m/z: 319 (M+1)+.

Workup

  1. stirringthe mixture was stirred at room temperature for 16 h
  2. extractionextracted with dichloromethane (100 mL×3)
  3. washThe organic phase was washed with sodium bicarbonate and brine
  4. concentrationconcentrated
  5. customThe crude product was purified by column chromatography (silica gel, petroleum ether/ethyl acetate 20:1 to 2:1)

Sources & evidence

ORD record
ord-381c6ffd2c4447ddb5ac0084cb7cdfed
Source dataset
uspto-grants-2012_01
Patent number
US08088760B2

Linked notes

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