2-Fluoro-5-iodopyridine → 7a-(6-Fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine

HRID 3298

반응식

HRID 3298 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][N:3]=1.[Li]C(C)(C)C.Cl([O-])(=O)(=O)=O.[CH2:19]1[C:26]2[CH2:25][CH2:24][CH2:23][N+:22]=2[CH2:21][CH2:20]1>CCOCC.CCCCC>[F:1][C:2]1[N:3]=[CH:4][C:5]([C:26]23[CH2:25][CH2:24][CH2:23][N:22]2[CH2:21][CH2:20][CH2:19]3)=[CH:6][CH:7]=1

참가 물질

6

반응물 3

HCID 27831792-Fluoro-5-iodopyridineHCID 10878400Pyrrolizinium, 1,2,3,5,6,7-hexahydro-, perchlorateHCID 178418306HCID 178418306, 화합물

생성물 1

HCID 189347457a-(6-Fluoro-3-pyridinyl)-hexahydro-1H-pyrrolizine수율 40.4%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 8003Pentane용매

반응 조건

온도
-78 °C

실험 절차

2-Fluoro-5-iodopyridine (200 μL, 0.90 mmol) was dissolved in Et2O and cooled to -78° C. A solution of 2.5M t-BuLi (1.2 mL, 1.98 mmol) in pentane was added, and the reaction was stirred for 2 minutes. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (375 mg, 1.80 mmol) was added, and the reaction mixture was allowed to stir for 10 minutes at -78° C. then allowed to warm to -20° C. The cold bath was removed, 2N HCl was added, and the mixture was extracted with Et2O. The phases were separated, and the aqueous phase was basified with 15% NaOH and extracted with CH2Cl2 (2×). The CH2 Cl2 fractions were combined, dried (MgSO4) and concentrated, and the residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford a clear oil (75 mg, 40%). 1H NMR (CDCl3, 300 MHz) δ1.58-1.73 (m, 2H), 1.79-2.05 (m, 6H), 2.64-2.73 (m, 2H), 3.12-3.19 (m, 2H), 6.82 (dd, J=8.4, 2.7 Hz, 1H), 7.90 (m, 1H), 8.30 (dd, J=1.4, 0.7 Hz, 1H); MS (CI/NH3) m/z: 207 (M+H)+.

후처리

  1. stirringto stir for 10 minutes at -78° C.
  2. temperatureto warm to -20° C
  3. customThe cold bath was removed
  4. addition2N HCl was added
  5. extractionthe mixture was extracted with Et2O
  6. customThe phases were separated
  7. extractionextracted with CH2Cl2 (2×)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customthe residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2)

출처 및 근거

ORD 기록
ord-d3051c784ee74eefb4384c960765bcf2
출처 데이터셋
uspto-grants-1998_03
특허 번호
US05733912

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