Dimethylformamide → 5-Fluoropyridine-3-carbonitrile

HRID 717546ノート

反応式

HRID 717546 の反応式
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([F:8])[CH:7]=1.[CH3:9][N:10](C)C=O>[C-]#N.[C-]#N.[Zn+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:8][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([CH:7]=1)[C:9]#[N:10]

参加物

6

反応物 2

HCID 6228DimethylformamideHCID 8202063-Bromo-5-fluoropyridine

生成物 1

HCID 224634715-Fluoropyridine-3-carbonitrile

試薬・触媒・溶媒 3

HCID 11186Zinc cyanide (Zn(CN)2)触媒HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒

反応条件

温度
130 °C

実験手順

Zn(CN)2 (2.45 g, 0.020 mol) and 1,1′-bis(diphenylphosphino)ferrocene (0.045 g, 0.0008 mol) were added to a solution of 3-bromo-5-fluoro pyridine (3.5 g, 0.0198 mol) in dimethylformamide. The reaction vessel was purged with argon for 10 min. Next, Pd2(dba)3 (0.04 g, 0.000043 mol) was added and the reaction vessel was purged with argon for another 5 min. The reaction mixture heated to 130° C. for 40 min under microwave irradiation. The reaction mixture was cooled to RT, diluted with water (100 mL) and extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with a saturated aqueous sodium chloride solution (2×100 mL) and dried over sodium sulphate. The combined organic layers were then concentrated under vacuum to get crude product, which was purified by silica gel column chromatography to afford 5-fluoronicotinonitrile. 1H NMR (400 MHz, CDCl3) δ 8.72 (s, 1H), 8.71-8.70 (d, J=4 Hz, 1H), 7.70-7.76 (d, J=4 Hz, 1H).

後処理

  1. customThe reaction vessel was purged with argon for 10 min
  2. customthe reaction vessel was purged with argon for another 5 min
  3. temperatureThe reaction mixture was cooled to RT
  4. additiondiluted with water (100 mL)
  5. extractionextracted with ethyl acetate (3×100 mL)
  6. washThe combined organic layers were washed with a saturated aqueous sodium chloride solution (2×100 mL)
  7. dry with materialdried over sodium sulphate
  8. concentrationThe combined organic layers were then concentrated under vacuum
  9. customto get crude product, which
  10. customwas purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-b704d110ee5e42bdade92d8551570d9f
出典データセット
uspto-grants-2015_11
特許番号
US09193724B2

反応ノート

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