Diisopropylamine → 7a-(2,6-Difluoro-3-pyridinyl)-hexahydro-1h-pyrrolizine

HRID 3293

反応式

HRID 3293 の反応式
[Li]CCCC.C(NC(C)C)(C)C.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[N:15]=1.Cl([O-])(=O)(=O)=O.[CH2:26]1[C:33]2[CH2:32][CH2:31][CH2:30][N+:29]=2[CH2:28][CH2:27]1>C1COCC1>[F:13][C:14]1[C:19]([C:33]23[CH2:32][CH2:31][CH2:30][N:29]2[CH2:28][CH2:27][CH2:26]3)=[CH:18][CH:17]=[C:16]([F:20])[N:15]=1

参加物

6

反応物 4

HCID 7912DiisopropylamineHCID 739342,6-DifluoropyridineHCID 10878400Pyrrolizinium, 1,2,3,5,6,7-hexahydro-, perchlorateHCID 178418339Butyllithium

生成物 1

HCID 189347437a-(2,6-Difluoro-3-pyridinyl)-hexahydro-1h-pyrrolizine収率 50.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

A solution of 2.5M nBuLi (675 μL, 1.7 mmol) in hexanes was added to diisopropylamine (220 μL, 1.6 mmol) in THF (4.5 mL) at ambient temperature. After 10 minutes of stirring, the reaction mixture was cooled to -78° C., 2,6-difluoropyridine (145 μL, 1.6 mmol) was introduced, and stirring was continued for 1 hour at -78° C. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (500 mg, 2.4 mmol) was then added, and the cold bath was removed. After warming to ambient temperature, a solution of 2N HCl was added and the phases were separated after pouting the reaction mixture over EtOAc. The aqueous phase was basified with 15% NaOH solution and extracted with CH2Cl2 (2×). The CH2Cl2 extracts were combined, dried (MgSO4), concentrated and chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford a clear oil (180 mg, 50%). MS (CI/NH3) m/e: 225 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.5-1.63 (m, 2H), 1.78-1.89 (m, 2H), 1.92-2.10 (m, 4H), 2.63-2.70 (m, 2H), 3.08-3.12 (m, 2H), 6.72 (dd, J=8.1, 3.0 Hz, 1H), 8.33 (dd, J=18.0, 8.1 Hz, 1H).

後処理

  1. stirringstirring
  2. waitwas continued for 1 hour at -78° C
  3. customthe cold bath was removed
  4. temperatureAfter warming to ambient temperature
  5. additiona solution of 2N HCl was added
  6. customthe phases were separated
  7. extractionextracted with CH2Cl2 (2×)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customchromatographed (silica gel; CHCl3 /MeOH, 98:2)

出典と根拠

ORDレコード
ord-d55b4270d2e84321a49a35cd7ef17438
出典データセット
uspto-grants-1998_03
特許番号
US05733912

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