1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (R)-2-Cyclopentyl-2-hydroxy-2-phenyl-1-piperazin-1-ylethanone

HRID 218040ノート

反応式

HRID 218040 の反応式
[CH:1]1([C@@:6]([OH:16])([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:7]([OH:9])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[N:17]1(C(OC(C)(C)C)=O)[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C(Cl)Cl>[CH:1]1([C@@:6]([OH:16])([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:7]([N:17]2[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1

参加物

7

反応物 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 948620alpha-Cyclopentylmandelic acid, (+)-

生成物 1

HCID 57613502(R)-2-Cyclopentyl-2-hydroxy-2-phenyl-1-piperazin-1-ylethanone収率 68.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a stirred solution of (R)-cyclopentylhydroxyphenyl acetic acid (10.0 g, 45.4 mmol) in DCM (200 mL) was added t-butyl 1-piperazinecarboxylate (8.5 g, 45.4 mmol). Into the reaction was added DIPEA (23.7 mL, 13.6 mmol), HOBt (10.4 g, 68.1 mmol), and then EDCI (10.4 g, 54.5 mmol). The mixture was stirred at room temperature for 12 hours. The mixture was then washed with 1N NaOH (300 mL), 1N HCl (300 mL) then saturated aqueous NaCl (300 mL). The organic layer was then removed, dried over MgSO4 and then filtered. The solvent was removed under reduced pressure. A solution of 20% TFA/DCM was added to the crude material, and the resulting mixture was stirred for 2 hours at room temperature. The solvent was removed under reduced pressure. DCM (300 mL) was added and the mixture was washed with saturated sodium bicarbonate (300 mL). The organic layer was then removed, dried over MgSO4 and filtered. The crude material was purified via silica gel chromatography (10% MeOH/DCM w/1% NH3 (aq)) to afford the title compound as a white powder (9.0 g, 31.2 mmol).

後処理

  1. washThe mixture was then washed with 1N NaOH (300 mL), 1N HCl (300 mL)
  2. customThe organic layer was then removed
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customThe solvent was removed under reduced pressure
  6. additionA solution of 20% TFA/DCM was added to the crude material
  7. stirringthe resulting mixture was stirred for 2 hours at room temperature
  8. customThe solvent was removed under reduced pressure
  9. additionDCM (300 mL) was added
  10. washthe mixture was washed with saturated sodium bicarbonate (300 mL)
  11. customThe organic layer was then removed
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. customThe crude material was purified via silica gel chromatography (10% MeOH/DCM w/1% NH3 (aq))

出典と根拠

ORDレコード
ord-7077b253aec64b349342b581183320ea
出典データセット
uspto-grants-2012_06
特許番号
US08198304B2

反応ノート

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