Diphenylacetaldehyde → (R)-1-(2-((2,2-Diphenylethenyl)oxy)ethyl)-3-piperidinecarboxylic acid ethyl ester

HRID 249432

Reaction equation

HRID 249432 reaction equation
[C:1]1([CH:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:8]=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br.[CH2:19]([O:21][C:22](=[O:32])[C@@H:23]1[CH2:28][CH2:27][CH2:26][N:25]([CH2:29][CH2:30]Br)[CH2:24]1)[CH3:20]>C1(C)C=CC=CC=1>[CH2:19]([O:21][C:22]([C@@H:23]1[CH2:28][CH2:27][CH2:26][N:25]([CH2:29][CH2:30][O:9][CH:8]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:24]1)=[O:32])[CH3:20]

Participants

5

Reactant 3

HCID 13696DiphenylacetaldehydeHCID 24758Sodium hydrideHCID 70009171(R)-1-(2-bromoethyl)nipecotic acid ethyl ester hydrobromide

Product 1

HCID 10621814(R)-1-(2-((2,2-Diphenylethenyl)oxy)ethyl)-3-piperidinecarboxylic acid ethyl esterYield 69.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Diphenylacetaldehyde (4.9 g, 0.025 mole) was added dropwise to a mixture of sodium hydride (1.5 g, 0.05 mole, 80% oil dispersion) and dry toluene (25 ml) at 0° C. This mixture was stirred at room temperature for 0.5 h, heated to 50° C. and allowed to cool to room temperature. The above (R)-1-(2-bromoethyl)nipecotic acid ethyl ester hydrobromide (8.6 g, 0.025 mole) was added portionwise whilst the temperature was kept below 30° C. with an ice-water bath. After being stirred for 1 h the reaction mixture was filtered, and the filtrate was evaporated to dryness. Flash chromatography of the residue on silica gel (200 g) using a mixture of heptane and tetrahydrofuran (4/1) as eluent provided the title compound (6.6 g, 69%) as an oil. Tlc: rf 0.24 (SiO2 ; heptane/THF 7/3).

Workup

  1. temperatureheated to 50° C.
  2. temperatureto cool to room temperature
  3. customwas kept below 30° C. with an ice-water bath
  4. stirringAfter being stirred for 1 h the reaction mixture
  5. filtrationwas filtered
  6. customthe filtrate was evaporated to dryness
  7. additiona mixture of heptane and tetrahydrofuran (4/1) as eluent

Sources & evidence

ORD record
ord-6008a16e2291462b970111ccd9e58c04
Source dataset
uspto-grants-1993_05
Patent number
US05214057

Linked notes

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