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

HRID 2226053Notes

Reaction equation

HRID 2226053 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 minutes. After the addition was completed, the ice-water bath was removed and the mixture was stirred an additional 4 hours while warming to ambient temperature. The solution was then poured into a separatory funnel containing 1 L of a 5% aqueous sodium hydroxide 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, 300 MHz) 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 hours
  5. temperaturewhile warming to ambient temperature
  6. additionThe solution was then poured into a separatory funnel
  7. additioncontaining 1 L of a 5% aqueous sodium hydroxide 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-ffb3e51dc12f45daac4ffa08289ae6bc
Source dataset
uspto-grants-1994_09
Patent number
US05344990

Reaction notes

Loading…