Water → 1,1-Dimethylethyl 4-[2-[[(methylsulfonyl)amino]methyl]phenyl]-1-piperazinecarboxylate

HRID 1419587Notes

Reaction equation

HRID 1419587 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[C:6]([O:10][C:11]([N:13]1[CH2:18][CH2:17][N:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH2:25][NH2:26])[CH2:15][CH2:14]1)=[O:12])([CH3:9])([CH3:8])[CH3:7].N1C=CC=CC=1.O>ClCCl>[C:6]([O:10][C:11]([N:13]1[CH2:14][CH2:15][N:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH2:25][NH:26][S:2]([CH3:1])(=[O:4])=[O:3])[CH2:17][CH2:18]1)=[O:12])([CH3:9])([CH3:7])[CH3:8]

Participants

6

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 31297Methanesulfonyl chloride2×HCID 4961274Tert-butyl 4-[2-(aminomethyl)phenyl]piperazine-1-carboxylate

Product 1

HCID 542677021,1-Dimethylethyl 4-[2-[[(methylsulfonyl)amino]methyl]phenyl]-1-piperazinecarboxylateYield 47%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methanesulfonyl chloride (0.186 mL, 275 mg, 2.4 mmol) was added dropwise to a stirred, cooled (0° C.) solution of 2-(4-t-butoxycarbonylpiperazin-1-yl)phenylmethylamine (0.58 g, 2 mmol) and pyridine (0.32 mL, 0.32 g, 4 mmol) in dichloromethane (10 mL) and the mixture was stirred at room temperature for 3 h. Further methanesulfonyl chloride (0.046 mL, 69 mg, 0.6 mmol) was added and the mixture was stirred at room temperature for 3 h. Water (1 mL) was added and the solvent was evaporated under reduced pressure. Aqueous sodium hydrogen carbonate (saturated, 20 mL) and water were added and the mixture was extracted with ethyl acetate (3×20 mL). The combined organic fractions were washed with aqueous citric acid (10%, 2×20 mL), aqueous sodium hydrogen carbonate (saturated, 2×20 mL) and brine (20 mL), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by MPLC on silica gel, eluting with CH2Cl2 /MeOH/NH3 (Aq.) (99:1:0.1) to give the title compound as a colorless solid (344 mg, 47%), δH (250 MHz, CDCl3) 7.33 (2H, m), 7.15 (2H, m), 5.80 (1H, br t, J 4.0 Hz), 4.40 (2H, d, J 4.0 Hz), 3.60 (4H, br t, J 3.4 Hz), 2.88 (4H, t, J 3.4 Hz), 2.82 (3H, s), and 1.49 (9H, s). m/e (ES+) 370 (MH+).

Workup

  1. stirringthe mixture was stirred at room temperature for 3 h
  2. customthe solvent was evaporated under reduced pressure
  3. additionAqueous sodium hydrogen carbonate (saturated, 20 mL) and water were added
  4. extractionthe mixture was extracted with ethyl acetate (3×20 mL)
  5. washThe combined organic fractions were washed with aqueous citric acid (10%, 2×20 mL), aqueous sodium hydrogen carbonate (saturated, 2×20 mL) and brine (20 mL)
  6. dry with materialdried (MgSO4)
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by MPLC on silica gel
  9. washeluting with CH2Cl2 /MeOH/NH3 (Aq.) (99:1:0.1)

Sources & evidence

ORD record
ord-ec5755a860524796aa7dbef67f78dd10
Source dataset
uspto-grants-1999_03
Patent number
US05885999

Reaction notes

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