HCID 131726048, compound → HCID 131726047, compound

HRID 1160352Notes

Reaction equation

HRID 1160352 reaction equation
[CH:1]([O:4][C:5]([C:7]1[C:12]([C:13]([CH3:21])([CH3:20])[O:14][SiH2:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[CH:11][CH:10]=[CH:9][N:8]=1)=[O:6])([CH3:3])[CH3:2].[H][H]>CO.O=[Pt]=O.[Rh]>[CH:1]([O:4][C:5]([C@H:7]1[C@@H:12]([C:13]([CH3:21])([CH3:20])[O:14][SiH2:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:11][CH2:10][CH2:9][NH:8]1)=[O:6])([CH3:3])[CH3:2]

Participants

6

Reactant 2

HCID 131726048HCID 131726048, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 131726047HCID 131726047, compound

Reagents, catalysts & solvents 3

HCID 23948RhodiumCatalystHCID 345198Adams' catalystCatalystHCID 887MethanolSolvent

Procedure

3-(tert-Butyldimethyl-silanyloxymethyl)-pyridine-2-carboxylic acid isopropyl ester (800 mg, 2.6 mmol) was dissolved in 6 mL of methanol in a pressure hydrogenation vessel to which 100 mg of PtO2 was added (Rh on alumina may also be used). The vessel was shaken under 50 psi of hydrogen for 5 hrs. The suspension was filtered through Celite and the solution was concentrated in vacuo to provide the desired compound, cis-3-(tert-butyl-dimethyl-silanyloxymethyl)-piperidine-2-carboxylic acid isopropyl ester. MS 316 (M+1). Without further purification the product was acylated under standard conditions with 1-(4-chloro-phenyl)-cyclobutanecarbonyl chloride (itself prepared from the carboxylic acid using excess thionyl chloride at reflux for 1 hr. followed by concentration in vacuo). Water/ether extractive workup gave, after concentration of the organic layers in vacuo and chromatography on silica gel, the desired compound, cis-3-(tert-Butyl-dimethyl-silanyloxymethyl)-1-[1-(4-chloro-phenyl)-cyclobutanecarbonyl]-piperidine-2-carboxylic acid isopropyl ester (720 mg, 55% for two steps) MS 508 (M+1). The cis stereochemistry was assigned based upon a 1H NMR coupling constant of 4 Hz for the proton at C-2 of the piperidine ring.

Workup

  1. filtrationThe suspension was filtered through Celite
  2. concentrationthe solution was concentrated in vacuo

Sources & evidence

ORD record
ord-b9470f7bca6244b8b7018f8a2b5198ab
Source dataset
uspto-grants-2010_10
Patent number
US07816375B2

Reaction notes

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