Ethyl Acetate → 1-Benzyl-4-(cyclopropylcarbonyl)piperazine

HRID 1972724Notes

Reaction equation

HRID 1972724 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:14]1([C:17](Cl)=[O:18])[CH2:16][CH2:15]1.C(N(C(C)C)CC)(C)C.CCOC(C)=O>ClCCCl>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:17]([CH:14]2[CH2:16][CH2:15]2)=[O:18])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 759941-BenzylpiperazineHCID 77637Cyclopropanecarbonyl chlorideHCID 81531Diisopropylethylamine

Product 1

HCID 12200501-Benzyl-4-(cyclopropylcarbonyl)piperazineYield 99.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 1-benzyl-piperazine (1.20 g, 6.81 mmol) in anhydrous DCE (23 mL) was added cyclopropane carboxylic acid chloride (854 mg, 8.17 mmol, 1.2 eq) followed by diisopropylethylamine (1.3 mL, 7.49 mmol, 1.1 eq), and the reaction mixture was stirred at 50° C. under N2 for 15 h. The mixture was cooled to rt and poured into EtOAc. The organic phase was washed with water and brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by MPLC (Biotage®, gradient elution 75% EtOAc/hexane) to give the product (1.65 g, 99%) as a brown oil. 1H-NMR (300 MHz, DMSO-d6) 7.34 to 7.23 (m, 5H), 3.64 (broad s, 2H), 3.48 (s, 2H), 3.44 (broad s, 2H), 2.37 (broad s, 2H), 2.28 (broad s, 2H), 1.95 to 1.91 (m, 1H), 0.70 to 0.65 (m, 4H); ES-MS m/z 245.2 [M+H]+, RT (min) 1.12.

Workup

  1. temperatureThe mixture was cooled to rt
  2. washThe organic phase was washed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by MPLC (Biotage®, gradient elution 75% EtOAc/hexane)

Sources & evidence

ORD record
ord-19e3b755b5bd4cd1aad2faf76f900693
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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