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

HRID 1697282ノート

反応式

HRID 1697282 の反応式
[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]

参加物

5

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 24462Copper Sulfate触媒HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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%))

出典と根拠

ORDレコード
ord-9a546efa9dd84831ae67829a4605c181
出典データセット
uspto-grants-2012_04
特許番号
US08163905B2

反応ノート

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