Dimethyl Sulfoxide → 4-Boc-1-Cbz-piperazine-2-carbaldehyde

HRID 70130Notes

Reaction equation

HRID 70130 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[OH:11][CH2:12][CH:13]1[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:16][CH2:15][N:14]1[C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27].C(N(CC)CC)C>C(Cl)Cl.O>[CH:12]([CH:13]1[CH2:18][N:17]([C:19]([O:21][C:22]([CH3:25])([CH3:23])[CH3:24])=[O:20])[CH2:16][CH2:15][N:14]1[C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27])=[O:11]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 235310394-(1,1-Dimethylethyl) 1-(phenylmethyl) 2-(hydroxymethyl)-1,4-piperazinedicarboxylate

Product 1

HCID 596715274-Boc-1-Cbz-piperazine-2-carbaldehyde

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

A solution of DMSO (1.41 mL, 19.9 mmol) in CH2Cl2 (5 mL) was added to a solution of oxalyl chloride (0.87 mL, 9.9 mmol) in CH2Cl2 (25 mL) at −60° C. After 5 min, a solution of 1-benzyl 4-tert-butyl 2-(hydroxymethyl)piperazine-1,4-dicarboxylate (3.16 g, 9.03 mmol) in CH2Cl2 (5 mL) was added. After 15 min., triethylamine (6.3 mL, 45 mmol) was added, and the reaction mixture was allowed to warm to rt. After 1 h, water (100 mL) was added, the organics were separated, and the aqueous layer was extracted with CH2Cl2 (3×100 mL). The combined organics were washed with brine (3×150 mL), 1% HCl (3×150 mL), water (150 mL), and 5% NaHCO3 (3×150 mL). The organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. This gave 3.07 g (98%) of the desired product as a thick oil. Rf=0.10 in 30% EtOAc/Hexane.

Workup

  1. waitAfter 15 min.
  2. waitAfter 1 h
  3. customthe organics were separated
  4. extractionthe aqueous layer was extracted with CH2Cl2 (3×100 mL)
  5. washThe combined organics were washed with brine (3×150 mL), 1% HCl (3×150 mL), water (150 mL), and 5% NaHCO3 (3×150 mL)
  6. dry with materialThe organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-09e2666dac3c444bbfbbff561221eb75
Source dataset
uspto-grants-2014_09
Patent number
US08822472B2

Reaction notes

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