Tert-butyl 4-(1-ethoxy-1-oxopropan-2-ylidene)piperidine-1-carboxylate → Ethyl 1-[(1,1-dimethylethoxy)carbonyl]-α-methyl-4-piperidineacetate

HRID 1374144Notes

Reaction equation

HRID 1374144 reaction equation
[CH2:1]([O:3][C:4](=[O:20])[C:5](=[C:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1)[CH3:6])[CH3:2]>CO.[H][H].[Pd]>[CH2:1]([O:3][C:4](=[O:20])[CH:5]([CH:7]1[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH2:11][CH2:12]1)[CH3:6])[CH3:2]

Participants

5

Reactant 1

HCID 59464295Tert-butyl 4-(1-ethoxy-1-oxopropan-2-ylidene)piperidine-1-carboxylate

Product 1

HCID 18670567Ethyl 1-[(1,1-dimethylethoxy)carbonyl]-α-methyl-4-piperidineacetateYield 96.4%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 178418361HCID 178418361, compoundSolvent

Procedure

To a solution of 765 mg of 2-(1-tert-butoxycarbonylpiperidin-4-ylidene)propionic acid ethyl ester (prepared following the method of synthesis as described in International Publication WO 99/40070) in 4 ml of methanol, 100 mg of 10% palladium-on-carbon was added, and stirred for 4 hours at room temperature, in hydrogen atmosphere. Then the reaction liquid was filtered and the filtrate was concentrated to provide 743 mg of 2-(1-tert-butoxycarbonylpiperidin-4-yl)propionic acid ethyl ester as a slightly yellowish oil. Of said product, 306 mg was dissolved in 9 ml of tetrahydrofuran and cooled to 0° C. To said tetrahydrofuran solution 150 mg of lithium aluminium hydride was added portionwise. The reaction liquid was stirred at 0° C. for an hour, sodium sulfate decahydrate was added thereto and the temperature was restored to room temperature, followed by an overnight's stirring. The reaction liquid was filtered, and the filtrate was concentrated to provide 313 mg of 2-(1-tert-butoxycarbonylpiperidin-4-yl)propanol as a yellowish oil. Of said oil, 210 mg was dissolved in 2 ml of dichloromethane and the solution was added to another −78° C. solution of 188 μl of oxaryl chloride and 359 μl of dimethylsulfoxide in dichloromethane (4 ml) over a period of 5 minutes. After 30 minutes' stirring, a solution of 993 μl of triethylamine in 0.5 ml of dichloromethane was added to the reaction liquid and the temperature of the system was restored to room temperature, followed by 25 minutes' stirring. After addition of water, the reaction liquid was extracted with ethyl acetate and the ethyl acetate layer was washed twice with water, dried over anhydrous sodium sulfate and concentrated to provide 163 mg of a pale yellow oil.

Workup

  1. customthe method of synthesis
  2. customThen the reaction liquid
  3. filtrationwas filtered
  4. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-ffb50ace1a0943c9a8be32414ac4cde5
Source dataset
uspto-grants-2007_01
Patent number
US07164024B2

Reaction notes

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