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

HRID 1481721Notes

Reaction equation

HRID 1481721 reaction equation
N1C=CC=CC=1.CS(C)=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].CCN(C(C)C)C(C)C>C(Cl)Cl>[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

6

Reactant 4

HCID 679Dimethyl Sulfoxide2×HCID 1049PyridineHCID 81531DiisopropylethylamineHCID 235310394-(1,1-Dimethylethyl) 1-(phenylmethyl) 2-(hydroxymethyl)-1,4-piperazinedicarboxylate

Product 1

HCID 596715274-Boc-1-Cbz-piperazine-2-carbaldehydeYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To SO3-pyr complex (5.84 g, 36.69 mmol) was added pyridine (2.90 mL, 36.66 mmol) and DMSO (7.20 mL, 101.37 mmol). Slurry was stirred at room temperature 10 min before DCM (30 mL) was added and mixture was cooled to 0° C. Then solution of 1-benzyl 4-tert-butyl 2-(hydroxymethyl)piperazine-1,4-dicarboxylate (6.44 g, 18.37 mmol), Hunig's base (11.0 mL, 63.15 mmol) and DMSO (7.20 mL, 101.37 mmol) in DCM (70 mL) was added over 10 min. Reaction mixture was stirred at 0° C. 30 min and TLC showed complete consumption of starting material. Reaction was washed subsequently with H2O (50 mL), cold aqueous 1N HCl (until aqueous phase stayed acidic), then NaHCO3 (aqueous saturated, 50 mL) and finally NaCl (aqueous saturated, 50 mL). Organic phase was dried over Na2SO4 and solvent concentrated. Crude 1-benzyl 4-tert-butyl 2-formylpiperazine-1,4-dicarboxylate (˜6.40 g, quant) was obtained as colorless oil and was taken directly into the next step.

Workup

  1. additionwas added
  2. customReaction mixture
  3. custom30 min and TLC
  4. customconsumption of starting material
  5. customReaction
  6. washwas washed subsequently with H2O (50 mL), cold aqueous 1N HCl (until aqueous phase stayed acidic)
  7. dry with materialOrganic phase was dried over Na2SO4 and solvent
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-5e3e4b5c4f29490d9a4f394f717a81df
Source dataset
uspto-grants-2016_08
Patent number
US09409905B2

Reaction notes

Loading…