Dimethyl Sulfoxide → tert-Butyl 4-formylpiperidine-1-carboxylate

HRID 380540Notes

Reaction equation

HRID 380540 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([CH2:24][OH:25])[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C(N(CC)CC)C>ClCCl>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([CH:24]=[O:25])[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 1.8 mL (20.4 mMol) oxalyl chloride in 180 mL dichloromethane was cooled to −60° C. at which point 2.9 mL (40.9 mMol) dimethylsulfoxide was added. After stirring for about 5 minutes, a solution of 4.0 gm (18.6 mmol) 1-tert-butoxycarbonyl-4-hydroxymethylpiperidine in dichloromethane was added. After stirring for 20 minutes, 12.9 mL (92.9) mmol triethylamine were added and the resulting solution was allowed to warm to room temperature and was stirred at that temperature for about an hour. The reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium chloride. The organic phase was washed sequentially with 5 N hydrochloric acid and saturated aqueous sodium chloride, dried over sodium sulfate, and concentrated under reduced pressure to provide 3.76 gm (95%) of the title compound as a yellow oil.

Workup

  1. additionwas added
  2. stirringAfter stirring for 20 minutes
  3. stirringwas stirred at that temperature for about an hour
  4. customThe reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium chloride
  5. washThe organic phase was washed sequentially with 5 N hydrochloric acid and saturated aqueous sodium chloride
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0696fe2a717f48f7948444f7913a451a
Source dataset
uspto-grants-2001_10
Patent number
US06303627B1

Reaction notes

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