trans-2-Phenyl-1-cyclopropanecarbonyl chloride → trans-(4-Cyclobutylpiperazin-1-yl)-(2-phenylcyclopropyl)methanone

HRID 572003Notes

Reaction equation

HRID 572003 reaction equation
Cl.Cl.[CH:3]1([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4]1.[C:13]1([C@@H:19]2[CH2:21][C@H:20]2[C:22](Cl)=[O:23])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.CCOC(C)=O.CCCCCC>C(Cl)Cl>[CH:3]1([N:7]2[CH2:12][CH2:11][N:10]([C:22]([C@@H:20]3[CH2:21][C@H:19]3[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[O:23])[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4]1

Participants

5

Reactant 3

HCID 13656trans-2-Phenyl-1-cyclopropanecarbonyl chlorideHCID 21226206Ethyl acetate hexaneHCID 451567991-Cyclobutylpiperazine dihydrochloride

Product 1

HCID 25196563trans-(4-Cyclobutylpiperazin-1-yl)-(2-phenylcyclopropyl)methanoneYield 57.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring slurry of 4A (130 mg, 0.610 mmol) in anhydrous DCM (3.5 mL) under an argon (g) atmosphere was added TEA (0.162 mL, 1.16 mmol). After 1 min. trans-2-phenyl-1-cyclopropanecarbonyl chloride (0.096 mL, 0.55 mmol) was added in one portion to the now clear solution. The reaction was left to stir for ca. 1.5 h at ambient temperature before being washed with H2O (2×2 mL), dilute aq. K2CO3 (1×2 mL), H2O (1×2 mL), dried over MgSO4, filtered and concentrated in vacuo. The resulting gum was subjected to flash chromatography (basic alumina-8 g; gradient elution: 5% EtOAc/Hexane for 1 min. then 5-55% EtOAc/Hexane over 7 min. at 18 mL/min) to afford 90 mg 4B as a white solid (57% yield). m/z (ES+) M+1=285.2; HPLC tR=1.54 min. 1H NMR (500 MHz, CDCl3) δ 7.29-7.24 (m, 2H), 7.20-7.16 (m, 1H), 7.10 (d, J=7.0 Hz, 2H), 3.80-3.46 (m, 4H), 2.72 (quintet, J=7.9 Hz, 1H), 2.47 (ddd, J=9.0, 6.3, 4.0 Hz, 1H), 2.39-2.25 (m, 4H), 2.08-1.98 (m, 2H), 1.95 (td, J=4.4, 3.7 Hz, 1H), 1.92-1.81 (m, 2H), 1.78-1.59 (m, 3H), 1.27-1.24 (m, 1H).

Workup

  1. waitThe reaction was left
  2. washbefore being washed with H2O (2×2 mL), dilute aq. K2CO3 (1×2 mL), H2O (1×2 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. washgradient elution
  7. wait5% EtOAc/Hexane for 1 min.

Sources & evidence

ORD record
ord-c73d4c1057ff41759fdbf0d2b89639ee
Source dataset
uspto-grants-2015_05
Patent number
US09029381B2

Reaction notes

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