Bromomethylcyclopropane → (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(cyclopropylmethoxy)butan-2-yl)piperidin-2-one

HRID 931954노트

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HRID 931954 반응식
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:24][CH3:25])[CH2:22][OH:23])[C:11](=[O:26])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.Br[CH2:28][CH:29]1[CH2:31][CH2:30]1.CC(C)([O-])C.[Na+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:24][CH3:25])[CH2:22][O:23][CH2:28][CH:29]3[CH2:31][CH2:30]3)[C:11](=[O:26])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1

참가 물질

5

반응물 3

HCID 81503BromomethylcyclopropaneHCID 23676156Sodium t-butoxideHCID 58573362(5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)piperidin-2-one

생성물 1

HCID 58573287(5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(cyclopropylmethoxy)butan-2-yl)piperidin-2-one

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
0 °C

실험 절차

To a solution of 1.48 g (3.77 mmol) of (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)piperidin-2-one (Example 68, Step A) and bromomethylcyclopropane (0.828 mL, 7.54 mmol) in DMF (20 mL) was added sodium t-butoxide (0.544 g, 5.66 mmol) at 0° C. The mixture was stirred at 0° C. for 2 h and then warmed to rt. Then the reaction was stirred at rt for 14 h. The reaction was quenched with sat. aqueous NH4Cl solution and extracted with EtOAc. The combined organic layers were washed with water and sat. aq. NaCl solution, dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure. Purification by flash chromatography on silica gel (eluent: 20%-40% EtOAc/Hexanes, gradient elution) provided the title compound as a colorless oil.

후처리

  1. temperaturewarmed to rt
  2. stirringThen the reaction was stirred at rt for 14 h
  3. customThe reaction was quenched with sat. aqueous NH4Cl solution
  4. extractionextracted with EtOAc
  5. washThe combined organic layers were washed with water and sat. aq. NaCl solution
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customPurification by flash chromatography on silica gel (eluent: 20%-40% EtOAc/Hexanes, gradient elution)

출처 및 근거

ORD 기록
ord-64bd22eb9c4545b08e92f2573456b6b0
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09296736B2

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