Methyl iodide → (2S,4S)-4-(dibenzylamino)-2-methylcyclohexanone (2R,4R)-4-(dibenzylamino)-2-methylcyclohexanone

HRID 1963904노트

반응식

HRID 1963904 반응식
[CH2:1]([N:8]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:9]1[CH2:14][CH2:13][C:12](=[O:15])[CH2:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:23][Si]([N-][Si](C)(C)C)(C)C.[K+].[C:33]1(C)C=CC=CC=1.C(B(CC)CC)C.IC.[OH-].[Na+]>C1COCC1>[CH2:16]([N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C@H:9]1[CH2:10][CH2:11][C:12](=[O:15])[C@@H:13]([CH3:23])[CH2:14]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[CH2:16]([N:8]([CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C@@H:9]1[CH2:10][CH2:11][C:12](=[O:15])[C@H:13]([CH3:33])[CH2:14]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

참가 물질

7

반응물 5

HCID 6328Methyl iodideHCID 7357TriethylboraneHCID 14798Sodium HydroxideHCID 220099024-(Dibenzylamino)cyclohexan-1-oneHCID 86583789KHMDS toluene

생성물 1

HCID 86650615(2S,4S)-4-(dibenzylamino)-2-methylcyclohexanone (2R,4R)-4-(dibenzylamino)-2-methylcyclohexanone

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A solution of 4-(dibenzylamino)cyclohexanone (4 g, 13.63 mmol) in THF (27 mL) was added to KHMDS/toluene (32.7 mL, 16.36 mmol) at ambient temperature. The mixture was stirred for 15 min at ambient temperature. Triethylborane (1M in THF, 17.72 mL, 17.72 mmol) was added dropwise and the mixture was allowed to stir an additional 30 min. Iodomethane (1.6 mL, 25.7 mmol) was added and the mixture was stirred for 20 hr at ambient temperature. Aqueous 1M NaOH solution was added (˜25 mL) and the mixture was vigorously stirred for 3 hr. The mixture was extracted with EtOAc (4ט100 mL) and the combined organic layers were washed with brine, dried over Na2SO4, filtered off, and concentrated in vacuo. The resulting residue was purified by column chromatography [SiO2, 125 g, EtOAc/hexane= 0/100 to 20/80]. Fractions were combined and concentrated in vacuo providing (2S,4S)-4-(dibenzylamino)-2-methylcyclohexanone/(2R,4R)-4-(dibenzylamino)-2-methylcyclohexanone as a highly viscous oil, which became partially a white solid. Yield: 3.1 g. LCMS (m/z): 308.2[M+H]+; Retention time=0.65 min (major isomer). Ratio major/minor isomer: ˜9:1.

후처리

  1. stirringto stir an additional 30 min
  2. stirringthe mixture was stirred for 20 hr at ambient temperature
  3. stirringthe mixture was vigorously stirred for 3 hr
  4. extractionThe mixture was extracted with EtOAc (4ט100 mL)
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered off
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was purified by column chromatography [SiO2, 125 g, EtOAc/hexane= 0/100 to 20/80]
  10. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-504117c3efad479f91f3471047bc646d
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08415381B2

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