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

HRID 278198Notes

Reaction equation

HRID 278198 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>C(Cl)Cl.C(OCC)(=O)C>[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

7

Reactant 4

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

Product 1

HCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateYield 85.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent4×HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 17.62 g (135.6 mmole) oxalyl chloride and 250 mL methylene chloride in a dry ice acetone bath was treated with a solution of 21.19 g (271.2 mmole) DMSO in 150 mL methylene chloride over 20 minutes. After stirring for 20 minutes, a solution of 24.327 g 1-(t-butoxycarbonyl)-4-hydroxymethylpiperidine (from Step B1 above) in 150 mL methylene chloride was added over 1 h. After an additional 15 minutes, 57.17 (565 mmole) triethylamine in 150 mL methylene chloride was added over half an hour. The reaction mixture was allowed to warm up over night in the cooling bath. The reaction mixture was concentrated under vacuum to remove about 400 mL methylene chloride, and the residue was partitioned between 1 L ether and 300 mL water. To this was added 200 mL 1 N NaOH, the layers were separated, and the organic layer was washed with 150 mL 1 N NaOH (2×), water (3×), and saturated brine, dried over sodium sulfate, and concentrated to give 22.562 g crude product. FC (10˜60% ethyl acetate in hexanes) gave 20.58 g title compound as slightly yellowish oil.

Workup

  1. waitAfter an additional 15 minutes
  2. temperatureto warm up over night in the cooling bath
  3. concentrationThe reaction mixture was concentrated under vacuum
  4. customto remove about 400 mL methylene chloride
  5. customthe residue was partitioned between 1 L ether and 300 mL water
  6. additionTo this was added 200 mL 1 N NaOH
  7. customthe layers were separated
  8. washthe organic layer was washed with 150 mL 1 N NaOH (2×), water (3×), and saturated brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated
  11. customto give 22.562 g crude product

Sources & evidence

ORD record
ord-49d8fc610908408d94ad3474655897e4
Source dataset
uspto-grants-2002_03
Patent number
US06358979B1

Reaction notes

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