Methyl iodide → (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(cyclopropylmethoxy)butan-2-yl)-3-methylpiperidin-2-one

HRID 931955노트

반응식

HRID 931955 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]([CH2:28][CH3:29])[CH2:22][O:23][CH2:24][CH:25]3[CH2:27][CH2:26]3)[C:11](=[O:30])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.IC.[CH3:33][Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[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]([CH2:28][CH3:29])[CH2:22][O:23][CH2:24][CH:25]3[CH2:27][CH2:26]3)[C:11](=[O:30])[CH:10]([CH3:33])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

참가 물질

5

반응물 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 58573287(5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(cyclopropylmethoxy)butan-2-yl)piperidin-2-one

생성물 1

HCID 67999671(5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(cyclopropylmethoxy)butan-2-yl)-3-methylpiperidin-2-one

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 0.325 g (0.73 mmol) of (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(cyclopropylmethoxy)butan-2-yl)piperidin-2-one (Example 68, Step B) and iodomethane (0.055 mL, 0.874 mmol) in THF (7.0 mL) was added lithium bis(trimethylsilyl) amide (1M solution in THF, 0.8 mL, 0.8 mmol) at −78° C. The reaction was allowed to warm to R.T., then 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. The crude material was absorbed onto a plug of silica gel and purified by chromatography on silica gel, eluting with a gradient of 10% to 30% EtOAc in hexane, to provide the title compound as a mixture of C-3 stereoisomers, as indicated by *.

후처리

  1. customwas quenched with sat. aqueous NH4Cl solution
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with water and sat. aq. NaCl solution
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe crude material was absorbed onto a plug of silica gel
  8. custompurified by chromatography on silica gel
  9. washeluting with a gradient of 10% to 30% EtOAc in hexane

출처 및 근거

ORD 기록
ord-c63bb5d978254beaa41efc73aeb1ba17
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09296736B2

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