Hydrochloric Acid → 7a-(2,6-dichloro-3-pyridinyl)-hexahydro-1H-pyrrolizine

HRID 3295

反応式

HRID 3295 の反応式
[Li]CCCC.C(NC(C)C)(C)C.[Cl:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl: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.Cl>C1COCC1.CCOC(C)=O>[Cl: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]([Cl:20])[N:15]=1

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 169892,6-DichloropyridineHCID 10878400Pyrrolizinium, 1,2,3,5,6,7-hexahydro-, perchlorateHCID 178418339Butyllithium

生成物 1

HCID 189347197a-(2,6-dichloro-3-pyridinyl)-hexahydro-1H-pyrrolizine収率 17.2%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate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, 1.7 mmol) in THF (4.5 mL) at ambient temperature. After 10 minutes of stirring, the reaction mixture was cooled to -78° C., 2,6-dichloropyridine (237 μL, 1.60 mmol) was added neat, and stirring was continued for 1 hour at -78° C. 1,2,3,5,6,7-hexahydropyrrolizinium perchlorate (500 mg, 2.40 mmol) was added, and the reaction mixture was allowed to stir for 2 hours at -78° C. then warm to ambient temperature. A solution of 2N HCl was added, and the mixture was then poured over EtOAc. The phases were separated, and the aqueous phase was basified with 15% NaOH and extracted with CH2Cl2 (2×). The CH2Cl2 fractions were combined, dried (MgSO4) and concentrated, and the residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2) to afford a clear oil (70.6 mg, 17%). MS (CI/NH3) m/e: 257/259 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ1.47-1.61 (m, 2H), 1.77-1.90 (m, 2H), 2.10-2.25 (m, 4H), 2.67-2.75 (m, 2H), 3.03-3.11 (m, 2H), 7.19 (d, J=8.5 Hz, 1H), 8.37 (d, J=8.5 Hz, 1H).

後処理

  1. stirringstirring
  2. waitwas continued for 1 hour at -78° C
  3. stirringto stir for 2 hours at -78° C.
  4. temperaturethen warm to ambient temperature
  5. customThe phases were separated
  6. extractionextracted with CH2Cl2 (2×)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customthe residue was chromatographed (silica gel; CHCl3 /MeOH, 98:2)

出典と根拠

ORDレコード
ord-c171067de28743cf9e9bdee6ad6c9574
出典データセット
uspto-grants-1998_03
特許番号
US05733912

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