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

HRID 1635954Notes

Reaction equation

HRID 1635954 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-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent4×HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 17.62 g (135.6 mmole) oxalyl chloride and 250 mL DCM in a dry ice acetone bath was treated with a solution of 21.19 g (271.2 mmole) DMSO in 150 mL DCM over 20 minutes. After stirring for 20 minutes, a solution of 24.327 g 1-(t-butoxycarbonyl)-4-hydroxymethyl-piperidine (from Step 1 above) in 150 mL DCM was added over one hour. After an additional 15 minutes, 57.17 g (565 mmole) triethylamine in 150 mL DCM was added over half an hour. The reaction mixture was allowed to warn up over night in the cooling bath. The reaction mixture was concentrated under vacuum to remove about 400 mL DCM, 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 crude product. FC (10˜60% ethyl acetate in hexanes) gave the title compound as slightly yellowish oil. RF: 0.29 (3:1 v/v hexanes/EtOAc); 1H NMR (500 MHz) δ 9.68 (d, J=0.7 Hz, 1H), 3.96˜4.02 (m, 2H), 2.92˜2.97 (m, 2H), 2.40˜2.45 (m, 1H), 1.88˜1.94 (m, 2H), 1.53˜1.64 (m, 2H), 1.47 (s, 9H).

Workup

  1. waitAfter an additional 15 minutes
  2. waitto warn up over night in the cooling bath
  3. concentrationThe reaction mixture was concentrated under vacuum
  4. customto remove about 400 mL DCM
  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 crude product

Sources & evidence

ORD record
ord-e94e207b52504293a8cbac1ab82de2b4
Source dataset
uspto-grants-2003_01
Patent number
US06511994B2

Reaction notes

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