Dimethyl Sulfoxide → (S)-1-(3-Benzyloxy-propyl)-3-methyl-piperazin-2-one

HRID 559349Notes

Reaction equation

HRID 559349 reaction equation
CS(C)=[O:3].C(Cl)(=O)[C:6](Cl)=[O:7].C(OC(=O)[NH:17][C@H:18]([C:20](=[O:36])[N:21]([CH2:25][CH2:26][CH2:27][O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:22][CH2:23]O)[CH3:19])(C)(C)C.C(N(CC)CC)C.C([SiH](CC)CC)C.FC(F)(F)C(O)=O.[Cl:59][CH2:60][Cl:61]>>[CH2:60]([Cl:61])[Cl:59].[CH3:6][OH:7].[NH4+:17].[OH-:3].[CH2:29]([O:28][CH2:27][CH2:26][CH2:25][N:21]1[CH2:22][CH2:23][NH:17][C@@H:18]([CH3:19])[C:20]1=[O:36])[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

9

Reactant 7

HCID 679Dimethyl SulfoxideHCID 6344Dichloromethane2×HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 12052TriethylsilaneHCID 65578Oxalyl chlorideHCID 66999069{(S)-1-[(3-Benzyloxy-propyl)(2-hydroxy-ethyl)-carbamoyl]-ethyl}-carbamic acid tert-butyl ester

Product 2

HCID 21896990Dichloromethane methanol ammonium hydroxideHCID 66999230(S)-1-(3-Benzyloxy-propyl)-3-methyl-piperazin-2-oneYield 78%

Procedure

Dimethyl sulfoxide (7.60 g, 97.2 mmol) was added dropwise at −78° C. to a solution of oxalyl chloride (6.17 g, 48.6 mmol) in dichloromethane (300 ml) then after 10 min a solution of {(S)-1-[(3-benzyloxy-propyl)-(2-hydroxy-ethyl)-carbamoyl]-ethyl}-carbamic acid tert-butyl ester (16.8 g, 44.2 mmol) in dichloromethane (300 ml) was added at a temperature below −70° C. After 1 h, triethylamine (16.1 g, 159 mmol) was added, then after 15 min the ice bath was removed. The reaction mixture was allowed to reach room temperature, then washed with sat. aq. sodium hydrogencarbonate solution and brine, dried (MgSO4), filtered, and evaporated. The residue was taken up in dichloromethane (300 ml), then triethylsilane (10.3 g, 88.4 mmol) and trifluoroacetic acid (75.6 g, 663 mmol) were added at room temperature. The reaction mixture was stirred at room temperature for 16 h, then evaporated. The residue wads dissolved in dichloromethane (100 ml), then triethylamine (60 ml) was added at 0° C. over 30 min, then after 45 min the reaction mixture was concentrated. The residue was dissolved in ethyl acetate and water, then 2 M aq. sodium carbonate solution was added under ice cooling. The organic layer was separated, washed with brine, dried (MgSO4), filtered, and evaporated. Chromatography (SiO2; CH2Cl2/MeOH/NH4OH 90:10:0.25) produced the title compound (9.07 g, 78%). Colorless oil, MS (ISP)-263.4 (M+H)+.

Workup

  1. customafter 15 min the ice bath was removed
  2. customto reach room temperature
  3. washwashed with sat. aq. sodium hydrogencarbonate solution and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customevaporated
  8. dissolutionThe residue wads dissolved in dichloromethane (100 ml)
  9. additiontriethylamine (60 ml) was added at 0° C. over 30 min
  10. concentrationafter 45 min the reaction mixture was concentrated
  11. dissolutionThe residue was dissolved in ethyl acetate
  12. additionwater, then 2 M aq. sodium carbonate solution was added under ice cooling
  13. customThe organic layer was separated
  14. washwashed with brine
  15. dry with materialdried (MgSO4)
  16. filtrationfiltered
  17. customevaporated

Sources & evidence

ORD record
ord-38a2f383afd74669b5b531e737585124
Source dataset
uspto-grants-2011_11
Patent number
US08063042B2

Reaction notes

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