Dimethyl Sulfoxide → 4-(tert-Butyl)-2-(1-Boc-piperidin-4-yloxy)benzaldehyde

HRID 644205Notes

Reaction equation

HRID 644205 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[C:11]([C:15]1[CH:22]=[CH:21][C:18]([CH2:19][OH:20])=[C:17]([O:23][CH:24]2[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]2)[CH:16]=1)([CH3:14])([CH3:13])[CH3:12].C(N(CC)CC)C>ClCCl>[C:11]([C:15]1[CH:22]=[CH:21][C:18]([CH:19]=[O:20])=[C:17]([O:23][CH:24]2[CH2:25][CH2:26][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:28][CH2:29]2)[CH:16]=1)([CH3:14])([CH3:12])[CH3:13]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 576024554-tert-Butyl-2-(1-Boc-piperidin-4-yloxy)benzyl Alcohol

Product 1

HCID 866342044-(tert-Butyl)-2-(1-Boc-piperidin-4-yloxy)benzaldehydeYield 101%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of oxalyl chloride (0.30 mL, 3.46 mmol) in dichloromethane (5 mL) stirring at −78° C. under nitrogen atmosphere, dimethylsulfoxide was added dropwise (0.49 mL, 6.93 mmol). After 10 min, a solution of the crude 4-(tert-butyl)-2-(1-Boc-piperidine-4-yloxy)benzyl alcohol (0.42 g, 1.15 mmol) in dichloromethane (6 mL) was added slowly via cannula. After the addition was complete, the reaction mixture was stirred at −78° C. for 1 h. The reaction was then treated with triethylamine (1.6 mL, 11.5 mmol) and allowed to warm up to room temperature overnight. The reaction mixture was partitioned between brine and dichloromethane. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried with magnesium sulfate, filtered, and concentrated in vacuo to a brown residue which was purified on a silica gel chromatotron plate. Elution with ethyl acetate-hexanes (1:5) afforded the title compound (0.42 g, 100%) as a clear oil which foamed up under vacuum.

Workup

  1. additionAfter the addition
  2. temperatureto warm up to room temperature overnight
  3. customThe reaction mixture was partitioned between brine and dichloromethane
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with dichloromethane
  6. dry with materialThe combined organic layers were dried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo to a brown residue which
  9. customwas purified on a silica gel chromatotron plate
  10. washElution with ethyl acetate-hexanes (1:5)

Sources & evidence

ORD record
ord-975771b404524465ad2dc41601721cb1
Source dataset
uspto-grants-2010_04
Patent number
US07700628B2

Reaction notes

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