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

HRID 1623329ノート

反応式

HRID 1623329 の反応式
[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

参加物

7

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-81b3a59d627d4af98cf85f255db41968
出典データセット
uspto-grants-2014_07
特許番号
US08778951B2

反応ノート

読み込み中…