Ethyl Acetate → phenylmethyl (2S)-4-[(3-bromophenyl)methyl]-2-methyl-1-piperazinecarboxylate

HRID 2080317Notes

Reaction equation

HRID 2080317 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][N:9]2[CH2:14][CH2:13][NH:12][C@@H:11]([CH3:15])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1.Cl[C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18].C(OCC)(=O)C.C([O-])(O)=O.[Na+]>CN(C1C=CN=CC=1)C.CS(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][N:9]2[CH2:14][CH2:13][N:12]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[C@@H:11]([CH3:15])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10387Benzyl chloroformateHCID 516892Sodium BicarbonateHCID 67101240(3S)-1-[(3-Bromophenyl)methyl]-3-methylpiperazine

Product 1

HCID 57730436phenylmethyl (2S)-4-[(3-bromophenyl)methyl]-2-methyl-1-piperazinecarboxylateYield 89.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of (3S)-1-[(3-Bromophenyl)methyl]-3-methylpiperazine (250 mg, 0.5 mmol), TEA (0.5 ml, 3.5 mmol), and DMAP (12 mg, 0.1 mmol) in 1 mL of dry DMSO was added dropwise benzyl chloroformate (0.34 mL, 2.25 mmol) at 10° C. while stirring. The mixture was then heated and stirred at 50° C. for 1.5 h. After cooling to room temperature, 15 mL of ethyl acetate and 5 mL of saturated NaHCO3 were added. The organic layer was separated, concentrated under vacuum and purified by Gilson reverse phase HPLC, eluting with acetonitrile/water/0.1% TFA (10/90 to 70/30, v/v, over 12 min), to give the title compound (180 mg, 70%). LC/MS: m/z, 403 (M+H), 1.74 min.

Workup

  1. temperatureThe mixture was then heated
  2. stirringstirred at 50° C. for 1.5 h
  3. customThe organic layer was separated
  4. concentrationconcentrated under vacuum
  5. custompurified by Gilson reverse phase HPLC
  6. washeluting with acetonitrile/water/0.1% TFA (10/90 to 70/30, v/v, over 12 min)

Sources & evidence

ORD record
ord-67213d1bbd5d47a7ab3298e689ed7985
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

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