2,5-Dimethylpiperazine, trans- → (+/-)-trans-1-(4-Bromo-alpha-(3-(tert-butyldimethylsilyloxy)phenyl)benzyl)-2,5-dimethylpiperazine

HRID 1460081Notes

Reaction equation

HRID 1460081 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](Cl)[C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH:10]=2)=[CH:4][CH:3]=1.[CH3:24][C@H:25]1[CH2:30][NH:29][C@H:28]([CH3:31])[CH2:27][NH:26]1>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:26]2[CH2:27][C@@H:28]([CH3:31])[NH:29][CH2:30][C@@H:25]2[CH3:24])[C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([O:15][Si:16]([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17])[CH:10]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 2206722,5-Dimethylpiperazine, trans-HCID 22350043alpha-(4-Bromophenyl)-3-(tert-butyldimethylsilyloxy)benzyl chloride

Product 1

HCID 69942830(+/-)-trans-1-(4-Bromo-alpha-(3-(tert-butyldimethylsilyloxy)phenyl)benzyl)-2,5-dimethylpiperazineYield 62%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

The crude benzhydryl chloride (approx. 135 mmol) was combined with 46.3 g (405 mmol) of trans-2,5-dimethylpiperazine (purified by recrystallization from toluene to mp=115°-119° C.) and 30 mL of toluene and heated at reflux overnight under nitrogen. The toluene was removed under vacuum, and the residue was redissolved in 2000 mL of diethyl ether and washed with 500 mL of 1.0M sodium hydroxide and 1000 mL of water. The ether solution was dried over sodium sulfate and the solvent removed to give a dark oil. The product was purified by chromatography on silica gel with 1-10% ethanol in dichloromethane to give 41.0 g (62%) of (±)-trans-1-(4-bromo-α-(3-(tert-butyldimethylsilyloxy)phenyl)benzyl)-2,5-dimethylpiperazine as a 1:1 mixture of diastereomers. NMR (300 MHz, CDCl3); δ 0.15 (s, 6H); 0.9 (m,12H); 1.2 (d,J=6 Hz,3H); 1.4-1.6 (m,2H); 2.2-3.0 (m,5H); 5.2 and 5.3 (s,1H); 6.6-7.5 (m,8H).

Workup

  1. temperatureheated
  2. temperatureat reflux overnight under nitrogen
  3. customThe toluene was removed under vacuum
  4. dissolutionthe residue was redissolved in 2000 mL of diethyl ether
  5. washwashed with 500 mL of 1.0M sodium hydroxide and 1000 mL of water
  6. dry with materialThe ether solution was dried over sodium sulfate
  7. customthe solvent removed
  8. customto give a dark oil
  9. customThe product was purified by chromatography on silica gel with 1-10% ethanol in dichloromethane

Sources & evidence

ORD record
ord-3abdb563125449f8a14e6a9546547234
Source dataset
uspto-grants-1998_12
Patent number
US05854249

Reaction notes

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