1-Methylpiperazine → Methyl α-[[(4-methyl-1-piperazinyl)sulfonyl]methyl]benzenepropanoate

HRID 1729259Notes

Reaction equation

HRID 1729259 reaction equation
[C:1]([CH:5]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[CH2:6][S:7](Cl)(=[O:9])=[O:8])([O:3][CH3:4])=[O:2].[CH3:18][N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1>ClCCl>[CH2:11]([CH:5]([CH2:6][S:7]([N:22]1[CH2:23][CH2:24][N:19]([CH3:18])[CH2:20][CH2:21]1)(=[O:9])=[O:8])[C:1]([O:3][CH3:4])=[O:2])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

4

Reactant 2

HCID 531671-MethylpiperazineHCID 22403010HCID 22403010, compound

Product 1

HCID 22402988Methyl α-[[(4-methyl-1-piperazinyl)sulfonyl]methyl]benzenepropanoateYield 81.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a 1 L round bottom flask was added the resultant compound from Example 1E (84.5 g, 0.305 mol) and dichloromethane (305 mL). The mixture was cooled to 0° C. in an ice water bath and a solution of N-methyl piperazine (35.5 mL, 32.1 g) dissolved in dichloromethane (305 mL) was added dropwise with vigorous stirring over 90 min. After the addition was completed, the ice-water bath was removed and the mixture was stirred an additional 4 h while warming to ambient temperature. The solution was then poured into a separatory funnel containing 1 L of a 5% aqueous NaOH solution. The layers were partitioned and the organic layer was dried over potassium carbonate. Concentration in vacuo yielded an oil, which was filtered through 200 g of silica gel using 4:1 hexane/ethyl acetate as an eluant. Concentration gave 84.3 g (81%) of the desired product as a yellow oil: IR (film); 1735, 1165, 955 cm-1 ; 1H NMR (CDCl3) δ 2.30 (s, 3H) , 2.42 (t, 4H, J=4.8) , 2.88 (dd, 1H, J=7.7, 14.0) , 2.93 (dd, 1H, J=3.7, 14.0) , 3.06 (dd, 1H, J=7.0, 13.6) , 3.18-3.27 (m, 5H) , 3.43 (dd, 1H, J=8.82, 13.9), 3.67 (s, 3H) , 7.14-7.17 (m, 2H) , 7.24-7.34 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 37.91, 42.22, 45.36, 45.83, 49.61, 52.21, 54.36, 127.06, 128.66, 128.92, 129.06, 136.79, 173.33.

Workup

  1. additionwas added dropwise
  2. additionAfter the addition
  3. customthe ice-water bath was removed
  4. stirringthe mixture was stirred an additional 4 h
  5. temperaturewhile warming to ambient temperature
  6. additionThe solution was then poured into a separatory funnel
  7. additioncontaining 1 L of a 5% aqueous NaOH solution
  8. customThe layers were partitioned
  9. dry with materialthe organic layer was dried over potassium carbonate
  10. concentrationConcentration in vacuo
  11. customyielded an oil, which
  12. filtrationwas filtered through 200 g of silica gel using 4:1 hexane/ethyl acetate as an eluant
  13. concentrationConcentration

Sources & evidence

ORD record
ord-720be390440644a79aa89450c5a529e0
Source dataset
uspto-grants-1994_07
Patent number
US05332742

Reaction notes

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