Hexachloroethane → 7a-(5-chloro-6-fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine

HRID 3327

반응식

HRID 3327 반응식
[Li]CCCC.C(NC(C)C)(C)C.[F:13][C:14]1[N:19]=[CH:18][C:17]([C:20]23[CH2:27][CH2:26][CH2:25][N:24]2[CH2:23][CH2:22][CH2:21]3)=[CH:16][CH:15]=1.[Cl:28]C(Cl)(Cl)C(Cl)(Cl)Cl>C1COCC1>[Cl:28][C:15]1[CH:16]=[C:17]([C:20]23[CH2:27][CH2:26][CH2:25][N:24]2[CH2:23][CH2:22][CH2:21]3)[CH:18]=[N:19][C:14]=1[F:13]

참가 물질

6

반응물 4

HCID 6214HexachloroethaneHCID 7912DiisopropylamineHCID 189347457a-(6-Fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizineHCID 178418339Butyllithium

생성물 1

HCID 189347597a-(5-chloro-6-fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine수율 34%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

n-BuLi (2.5M in hexanes, 0.232 mL, 0.58 mmol) was added to di-isopropylamine (0.077 mL, 0.58 mmol) in THF and stirred at room temperature for 15 minutes, then cooled to -78° C. 7a-(6-Fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine (115 mg, 0.56 mmol, from Example 12d) and hexachloroethane (400 mg, 1.7 mmol) were added. The mixture was slowly warmed to room temperature and stirred overnight. The reaction was quenched with 2N HCl, and the mixture was washed with Et2O. The aqueous layer was basified with 15% NaOH and extracted with methylene chloride. The organic extracts were combined, dried, (MgSO4) and concentrated. The residue was chromatographed (silica gel; CHCl3 /MeOH, 99:1) to afford the title compound as an oil (45 mg, 34%): 1H NMR (CDCl3, 300 MHz) δ1.60-1.72 (m, 2H), 1.80-2.06 (m, 6H), 2.64-2.72 (m, 2H), 3.14-3.27 (m, 2H), 8.00 (dd, J=8.8, 2.0 Hz, 1H), 8.15 (dd, J=2.0, 1.0 Hz, 1H); MS (CI/NH3) m/z: 241 (M+H)+.

후처리

  1. temperaturecooled to -78° C
  2. temperatureThe mixture was slowly warmed to room temperature
  3. stirringstirred overnight
  4. customThe reaction was quenched with 2N HCl
  5. washthe mixture was washed with Et2O
  6. extractionextracted with methylene chloride
  7. customdried
  8. concentration(MgSO4) and concentrated
  9. customThe residue was chromatographed (silica gel; CHCl3 /MeOH, 99:1)

출처 및 근거

ORD 기록
ord-00bd9856a1bd4532834dd176039f25ee
출처 데이터셋
uspto-grants-1998_03
특허 번호
US05733912

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