Potassium sodium tartarate → (1-(5-Bromo-3-chloropyridin-2-yl)cyclopropyl)methanamine

HRID 578862ノート

反応式

HRID 578862 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([Cl:13])[C:5]([C:8]2([C:11]#[N:12])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[H-].C([Al+]CC(C)C)C(C)C.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([Cl:13])[C:5]([C:8]2([CH2:11][NH2:12])[CH2:9][CH2:10]2)=[N:6][CH:7]=1

参加物

5

反応物 3

HCID 9855836Potassium sodium tartarateHCID 21225700Diisobutylaluminumhydride2 回HCID 715592791-(5-Bromo-3-chloropyridin-2-yl)cyclopropane-1-carbonitrile

生成物 1

HCID 89544163(1-(5-Bromo-3-chloropyridin-2-yl)cyclopropyl)methanamine収率 46.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
-78 °C

実験手順

106 mg of 1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropanecarbonitrile (step 2) was dissolved in 2 ml of dichloromethane and was cooled down to −78° C. Then 0.91 ml of diisobutylaluminium hydride (1M in tetrahydrofuran) was added dropwise. The reaction mixture was stirred at −78° C. for 1 h, then at ambient temperature for three days. Then 0.40 ml of diisobutylaluminium hydride solution was added again at −78° C. and the reaction mixture was warmed to 40° C. and stirred for 24 hours. The reaction mixture was poured into a saturated solution of potassium sodium tartrate and the resulting mixture was stirred for 1 hour. The aqueous phase was extracted with three 25 ml portions dichloromethane. The organic phase was dried over sodium sulfate, filtered and concentrated. 140 mg of crude material was obtained as a yellow sticky solid. The residue was partitioned between 1N aqueous hydrochloric acid and ethyl acetate. The aqueous phase was adjusted to pH 14 by addition of an aqueous solution of sodium hydroxide and extracted with ethyl acetate. The organic phase was dried over sodium sulfate, filtered and concentrated. Thus, 50 mg of C-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropyl]-methylamine was obtained as a yellow sticky solid. 1H-NMR (CDCl3): 8.50 ppm (s, 1H), 7.83 ppm (s, 1H), 2.95 ppm (s, 2H), 1.40 ppm (s, 2H, broad), 0.99 ppm (m, 2H), 0.90 ppm (m, 2H).

後処理

  1. waitat ambient temperature for three days
  2. temperaturethe reaction mixture was warmed to 40° C.
  3. stirringstirred for 24 hours
  4. stirringthe resulting mixture was stirred for 1 hour
  5. extractionThe aqueous phase was extracted with three 25 ml portions dichloromethane
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custom140 mg of crude material was obtained as a yellow sticky solid
  10. customThe residue was partitioned between 1N aqueous hydrochloric acid and ethyl acetate
  11. additionThe aqueous phase was adjusted to pH 14 by addition of an aqueous solution of sodium hydroxide
  12. extractionextracted with ethyl acetate
  13. dry with materialThe organic phase was dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated

出典と根拠

ORDレコード
ord-5090ee14e0b34473be771d627986bb7d
出典データセット
uspto-grants-2015_05
特許番号
US09040708B2

反応ノート

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