Water → 2-Fluoro-3-(pyrimidin-5-yl)benzonitrile

HRID 871147ノート

反応式

HRID 871147 の反応式
Br[C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:14]([C:16]1[C:17]([F:25])=[C:18](B(O)O)[CH:19]=[CH:20][CH:21]=1)#[N:15].O>COCCOC.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCO>[F:25][C:17]1[C:18]([C:2]2[CH:3]=[N:4][CH:5]=[N:6][CH:7]=2)=[CH:19][CH:20]=[CH:21][C:16]=1[C:14]#[N:15]

参加物

8

反応物 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 783445-BromopyrimidineHCID 445581733-Cyano-2-fluorobenzeneboronic acid

生成物 1

HCID 867304012-Fluoro-3-(pyrimidin-5-yl)benzonitrile収率 24%

試薬・触媒・溶媒 3

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 702Ethanol溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
70 °C

実験手順

A sealed tube apparatus was charged with a solution containing 5-bromopyrimidine (1 g, 6.29 mmol), sodium carbonate (3.33 g, 31.4 mmol), and 3-cyano-2-fluorophenylboronic acid (1.037 g, 6.29 mmol) in a mixture of DME (Ratio: 2, Volume: 31.4 ml), water (Ratio: 1.000, Volume: 15.72 ml), and EtOH (Ratio: 1.000, Volume: 15.72 ml) at ambient temperature. Tetrakis(triphenylphosphine) palladium(0) (0.363 g, 0.314 mmol) was then added and the system was purged with nitrogen, sealed, and heated to 70° C. for 12 h. The vessel was cooled to room temperature and diluted with EtOAc and water. The mixture was further diluted with brine and extracted three times with EtOAc. The combined organics were dried over MgSO4, filtered, and concentrated to give the crude product. The crude material was purified by flash chromatography on silica using an ISCO machine (40 g SiO2 column, 40 mL/min, 0-40% EtOAc/hexanes over 15 minutes, tr=8 minutes) to afford the title compound (300 mg, 24%). ESI MS (M+H)+=200.0. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.28 (1 hr, s), 9.09 (2 hr, d, J=1.54 Hz), 8.02-8.12 (2 hr, m), 7.59 (1 hr, t, J=7.81 Hz).

後処理

  1. additionA sealed tube apparatus was charged with a solution
  2. customthe system was purged with nitrogen
  3. customsealed
  4. temperatureThe vessel was cooled to room temperature
  5. additiondiluted with EtOAc and water
  6. additionThe mixture was further diluted with brine
  7. extractionextracted three times with EtOAc
  8. dry with materialThe combined organics were dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give the crude product
  12. customThe crude material was purified by flash chromatography on silica using an ISCO machine (40 g SiO2 column, 40 mL/min, 0-40% EtOAc/hexanes over 15 minutes, tr=8 minutes)

出典と根拠

ORDレコード
ord-92bcf948fbf647baa4914692874e6866
出典データセット
uspto-grants-2015_03
特許番号
US08969586B2

反応ノート

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