Triethylamine → N-(((2R)-1,4-dibenzyl-2-piperazinyl)methyl)-N-phenylmethanesulfonamide

HRID 1972615Notes

Reaction equation

HRID 1972615 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][C@@H:9]1[CH2:21][NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:36][S:37](Cl)(=[O:39])=[O:38]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:10][C@@H:9]1[CH2:21][N:22]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[S:37]([CH3:36])(=[O:39])=[O:38])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 8471Triethylamine2×HCID 31297Methanesulfonyl chloride2×HCID 66584230N-(((2S)-1,4-dibenzyl-2-piperazinyl)methyl)aniline

Product 1

HCID 66582506N-(((2R)-1,4-dibenzyl-2-piperazinyl)methyl)-N-phenylmethanesulfonamideYield 59.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A 250-mL round-bottomed flask was charged with N-(((2S)-1,4-dibenzyl-2-piperazinyl)methyl)aniline (0.734 g, 1.98 mmol), DMAP (0.027 g, 0.22 mmol), triethylamine (0.85 mL, 6.1 mmol) and CH2Cl2 (8 mL). Methanesulfonyl chloride (0.23 mL, 3.0 mmol) was added drop wise at room temperature and the mixture was stirred at room temperature for 2 h. Additional methanesulfonyl chloride (0.20 mL, 2.6 mmol) and triethylamine (1.0 mL, 7.2 mmol) were added. The mixture was stirred at room temperature for another 1.5 h and then the mixture was concentrated to half the original volume and partitioned between water (40 mL) and EtOAc (40 mL). The aqueous phase was extracted with EtOAc (30 mL). The combined organic phases were washed with saturated aqueous NaCl (50 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (25 g of silica gel, 0 to 60% EtOAc in hexanes) to afford N-(((2R)-1,4-dibenzyl-2-piperazinyl)methyl)-N-phenylmethanesulfonamide (0.528 g) as a light yellow solid.

Workup

  1. stirringThe mixture was stirred at room temperature for another 1.5 h
  2. concentrationthe mixture was concentrated to half the original volume
  3. custompartitioned between water (40 mL) and EtOAc (40 mL)
  4. extractionThe aqueous phase was extracted with EtOAc (30 mL)
  5. washThe combined organic phases were washed with saturated aqueous NaCl (50 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by column chromatography (25 g of silica gel, 0 to 60% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2a1b8d0765d84ce985f7bea86b78cc67
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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