Water → 2-Chloro-1-(4-(4-chloro-3-methoxyphenyl)piperazin-1-yl)ethanone

HRID 2422757Notes

Reaction equation

HRID 2422757 reaction equation
Cl.Cl.[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:6][C:5]=1[O:16][CH3:17].O.C([O-])([O-])=O.[K+].[K+].[Cl:25][CH2:26][C:27](Cl)=[O:28]>C(Cl)Cl>[Cl:25][CH2:26][C:27]([N:13]1[CH2:12][CH2:11][N:10]([C:7]2[CH:8]=[CH:9][C:4]([Cl:3])=[C:5]([O:16][CH3:17])[CH:6]=2)[CH2:15][CH2:14]1)=[O:28]

Participants

6

Reactant 4

HCID 962WaterHCID 6577Chloroacetyl chlorideHCID 11430Potassium CarbonateHCID 671038731-(4-Chloro-3-methoxyphenyl)piperazine dihydrochloride

Product 1

HCID 210711262-Chloro-1-(4-(4-chloro-3-methoxyphenyl)piperazin-1-yl)ethanoneYield 185.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
5 °C

Procedure

To a 3 L flask equipped with a mechanical stirrer was added 1-(4-chloro-3-methoxyphenyl)piperazine dihydrochloride (220 g, 0.73 mol, 1 equiv), CH2Cl2 (1000 mL), and water (1000 mL). The biphasic mixture was cooled to 5° C. with an ice-water bath. K2CO3 (506 g, 5 equiv) was added to the vigorously stirring solution in portions to minimize foaming. A solution of chloroacetyl chloride (124.4 g, 1.5 equiv) in CH2Cl2 (100 mL) was added dropwise from an addition funnel, while maintaining an internal temperature below 8° C. After 1 h, the cooling bath was removed, and the reaction warmed to room temperature. After an additional 1 h, the layers were partitioned. The aqueous phase was extracted with CH2Cl2 (2×300 mL), and the combined organic layers dried over 3:1 Na2SO4/K2CO3 (addition of K2CO3 helps the solution phase to become clear). After filtration, the filtrate was concentrated in vacuo, and the residue was dried for 16 h under vacuum to afford the product as an off-white solid (410 g, 92% yield).

Workup

  1. customTo a 3 L flask equipped with a mechanical stirrer
  2. temperaturewhile maintaining an internal temperature below 8° C
  3. customthe cooling bath was removed
  4. temperaturethe reaction warmed to room temperature
  5. waitAfter an additional 1 h
  6. customthe layers were partitioned
  7. extractionThe aqueous phase was extracted with CH2Cl2 (2×300 mL)
  8. dry with materialthe combined organic layers dried over 3:1 Na2SO4/K2CO3 (
  9. additionaddition of K2CO3
  10. filtrationAfter filtration
  11. concentrationthe filtrate was concentrated in vacuo
  12. customthe residue was dried for 16 h under vacuum

Sources & evidence

ORD record
ord-9bfe91a3145c49d0b266382707788d5c
Source dataset
uspto-grants-2011_06
Patent number
US07960388B2

Reaction notes

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