Dimethyl Sulfoxide → 4-Benzyl 1-(tert-butyl) (R)-2-formylpiperazine-1,4-dicarboxylate

HRID 1006350Notes

Reaction equation

HRID 1006350 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])[CH2:20][C@H:19]1[CH2:34][OH:35])=[O:17])([CH3:14])([CH3:13])[CH3:12].[Cl-].[NH4+]>ClCCl.C(N(CC)CC)C>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][CH2:27][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[O:25])[CH2:20][C@@H:19]1[CH:34]=[O:35])=[O:17])([CH3:14])([CH3:13])[CH3:12]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 25517Ammonium ChlorideHCID 65578Oxalyl chlorideHCID 69745232(S)-4-benzyl 1-tert-butyl 2-(hydroxymethyl)piperazine-1,4-dicarboxylate

Product 1

HCID 865896504-Benzyl 1-(tert-butyl) (R)-2-formylpiperazine-1,4-dicarboxylateYield 101.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8471TriethylamineSolvent

Procedure

Under nitrogen atmosphere, to a solution of oxalyl chloride (1.64 ml) in dichloromethane (34 ml) under −65° C., was added dropwise a solution of dimethyl sulfoxide (2.0 ml) in dichloromethane (15 ml) and stirred for 10 minutes at the same temperature. A solution of (2S)-2-(hydroxymethyl)piperazine-1,4-dicarboxylic acid 4-benzyl ester 1-tert-butyl ester (3.29 g) in dichloromethane (24 ml) was dropped into the above solution over 5 minutes under −65° C. The reaction mixture was stirred at the same temperature for 15 minutes, then stirred at −45° C. for 90 minutes. Triethylamine (7.85 ml) was added to the solution under −40° C., and the mixture was stirred at 0° C. for 20 minutes. The mixture was poured into saturated aqueous ammonium chloride (100 ml). The organic layer was washed with brine, dried over magnesium sulfate, and evaporated to give (2R)-2-formylpiperazine-1,4-dicarboxylic acid 4-benzyl ester 1-tert-butyl ester (3.33 g) as a colorless syrup.

Workup

  1. stirringThe reaction mixture was stirred at the same temperature for 15 minutes
  2. stirringstirred at −45° C. for 90 minutes
  3. stirringthe mixture was stirred at 0° C. for 20 minutes
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated

Sources & evidence

ORD record
ord-766c0620e8f846868cc5100564247243
Source dataset
uspto-grants-2004_09
Patent number
US06787543B2

Reaction notes

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