Dimethyl Sulfoxide → 1-(2-Trimethylsilyl(ethanesulfonyl))piperidine-3-carbaldehyde

HRID 2355313Notes

Reaction equation

HRID 2355313 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH3:11][Si:12]([CH3:27])([CH3:26])[CH2:13][CH2:14][S:15]([N:18]1[CH2:23][CH2:22][CH2:21][CH:20]([CH2:24][OH:25])[CH2:19]1)(=[O:17])=[O:16].C(N(CC)CC)C>C(Cl)Cl>[CH3:11][Si:12]([CH3:27])([CH3:26])[CH2:13][CH2:14][S:15]([N:18]1[CH2:23][CH2:22][CH2:21][CH:20]([CH:24]=[O:25])[CH2:19]1)(=[O:17])=[O:16]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chloride2×HCID 59383010(1-(2-(Trimethylsilyl)ethylsulfonyl)piperidin-3-yl)methanol

Product 1

HCID 593830221-(2-Trimethylsilyl(ethanesulfonyl))piperidine-3-carbaldehydeYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

A three neck 500-mL flask equipped with a dropping funnel was charged with of anhydrous CH2Cl2 (100 mL) and oxalyl chloride (2.64 g, 20.7 mmol, 1.1 equiv). The solution was cooled to −78° C. under nitrogen. A solution of DMSO (2.93 g, 37.6 mmol, 2.0 equiv) in CH2Cl2 (10 mL) was added dropwise to the oxalyl chloride over a 15 minute period, and the resulting solution stirred for 30 min at −78° C. A solution of 1-(2-(trimethylsilyl)ethanesulfonyl)-3-hydroxymethylpiperidine (5.25 g, 18.8 mmol, 1.0 equiv) in CH2Cl2 (30 mL) was added dropwise over a 30 min period, and the resulting mixture stirred for 30 min at −78° C. Triethylamine (9.51 g, 94.4 mmol, 5.0 equiv) was added dropwise to the mixture over a 30 min period. The resulting white slurry was allowed to warm to 0° C. and stir for 30 min. Analysis of the mixture by LC-MS showed consumption of the alcohol. Water (200 mL) was added and the layers were separated. The organic layer was washed with brine and dried over Na2SO4. The aldehyde was purified by flash chromatography on 120 g of silica, eluting with 0 to 50% EtOAc in hexanes. Fractions containing the desired aldehyde were visualized by staining with 2,4-dinitrophenylhydrazine on silica gel. Removal of the solvent afforded 1-(2-trimethylsilyl(ethanesulfonyl))piperidine-3-carbaldehyde (3.81 g, 73%) as a white solid. 1H NMR (CDCl3) δ−0.15 (s, 9H), 0.96 (m, 2H), 1.5-1.77 (m, 4H), 1.95 (M, 1H), 2.54 (m, 1H), 2.82 (m, 2H), 2.95 (m, 1H), 3.17 (d of d, 1H), 3.44 (m, 1H), 3.72 (m, 1H), 9.64 (s, 1H).

Workup

  1. customA three neck 500-mL flask equipped with a dropping funnel
  2. stirringthe resulting mixture stirred for 30 min at −78° C
  3. temperatureto warm to 0° C.
  4. stirringstir for 30 min
  5. customconsumption of the alcohol
  6. additionWater (200 mL) was added
  7. customthe layers were separated
  8. washThe organic layer was washed with brine
  9. dry with materialdried over Na2SO4
  10. customThe aldehyde was purified by flash chromatography on 120 g of silica
  11. washeluting with 0 to 50% EtOAc in hexanes
  12. additionFractions containing the desired aldehyde
  13. customRemoval of the solvent

Sources & evidence

ORD record
ord-5ab03a635b184efe83ed6eccbfc4ad5f
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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