Benzyl 4-formylpiperidine-1-carboxylate → 4-[(R)-[[(R)-(1,1-Dimethylethyl)sulfinyl]amino]phenylmethyl]-1-piperidinecarboxylic acid, phenylmethyl ester

HRID 2070701Notes

Reaction equation

HRID 2070701 reaction equation
[CH:1]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:5][CH2:4]1)=O.[CH3:19][C:20]([S@:23]([NH2:25])=[O:24])([CH3:22])[CH3:21]>S([O-])([O-])(=O)=O.[Cu+2].ClCCl>[CH3:19][C:20]([S@:23]([NH:25][C@@H:1]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:5][CH2:4]1)=[O:24])([CH3:22])[CH3:21]

Participants

5

Reactant 2

HCID 2776272Benzyl 4-formylpiperidine-1-carboxylateHCID 10964479tert-Butylsulfinamide, (R)-(+)-

Product 1

HCID 866632334-[(R)-[[(R)-(1,1-Dimethylethyl)sulfinyl]amino]phenylmethyl]-1-piperidinecarboxylic acid, phenylmethyl esterYield 74.9%

Reagents, catalysts & solvents 2

HCID 24462Copper SulfateCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-formyl-piperidine-1-carboxylic acid, benzyl ester (0.96 g), (R)-2-methyl-2-propanesulfinamide (0.51 g), anhydrous copper(II) sulphate (1.5 g) and dichloromethane (20 mL) was stirred at room temperature for 48 h. Copper(II) sulphate was filtered off and the filtrate concentrated. The residue was treated with dry dichloromethane (15 mL) and cooled to −78° C. A solution of phenylmagnesium bromide in diethyl ether (3M, 4 mL) was added dropwise. The mixture was slowly warmed to 0° C., then quenched with sat. aqueous NH4Cl solution. The mixture was stirred for 15 min and extracted into dichloromethane. The organic phase was dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified (SiO2 chromatography eluting with iso-hexane:ethyl acetate (0-100%)) to give the title compound (623 mg).

Workup

  1. filtrationCopper(II) sulphate was filtered off
  2. concentrationthe filtrate concentrated
  3. additionThe residue was treated with dry dichloromethane (15 mL)
  4. temperaturecooled to −78° C
  5. additionA solution of phenylmagnesium bromide in diethyl ether (3M, 4 mL) was added dropwise
  6. temperatureThe mixture was slowly warmed to 0° C.
  7. customquenched with sat. aqueous NH4Cl solution
  8. stirringThe mixture was stirred for 15 min
  9. extractionextracted into dichloromethane
  10. dry with materialThe organic phase was dried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified
  14. wash(SiO2 chromatography eluting with iso-hexane:ethyl acetate (0-100%))

Sources & evidence

ORD record
ord-e657823b408a42f7a19886e6ac7dee8c
Source dataset
uspto-grants-2012_10
Patent number
US08299246B2

Reaction notes

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