Dimethylformamide → 3-(4,4-dimethyl-2-oxo-2,4-dihydro-1H-benzo[d][1,3]oxazin-6-yl)-5-fluorobenzonitrile

HRID 50674

反応式

HRID 50674 の反応式
Br[C:2]1[CH:3]=[C:4]([C:9]2[CH:21]=[CH:20][C:12]3[NH:13][C:14](=[O:19])[O:15][C:16]([CH3:18])([CH3:17])[C:11]=3[CH:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.[CH3:22][N:23](C=O)C>[C-]#N.[Zn+2].[C-]#N.[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>[CH3:17][C:16]1([CH3:18])[O:15][C:14](=[O:19])[NH:13][C:12]2[CH:20]=[CH:21][C:9]([C:4]3[CH:3]=[C:2]([CH:7]=[C:6]([F:8])[CH:5]=3)[C:22]#[N:23])=[CH:10][C:11]1=2

参加物

5

反応物 2

HCID 6228DimethylformamideHCID 98098756-(3-Bromo-5-fluorophenyl)-4,4-dimethyl-1,4-dihydrobenzo[d][1,3]oxazin-2-one

生成物 1

HCID 98391343-(4,4-dimethyl-2-oxo-2,4-dihydro-1H-benzo[d][1,3]oxazin-6-yl)-5-fluorobenzonitrile

試薬・触媒・溶媒 2

HCID 11186Zinc cyanide (Zn(CN)2)触媒HCID 11979704Tetrakis(triphenylphosphine)palladium触媒

反応条件

温度
85 °C

実験手順

A mixture of 6-(3-bromo-5-fluorophenyl)-4,4-dimethyl-2H-benzo[d][1,3]oxazin-2-one (1 g, 2.8 mmol), zinc cyanide (0.2 g, 1.7 mmol), and tetrakis(triphenylphosphine)-palladium (0) (0.2 g, 0.17 mmol) in dry DMF (20 mL) was degassed to remove oxygen and then was heated at 85° C. under a blanket of nitrogen for 6.5 hours. The reaction solution was cooled to room temperature and poured onto a cold saturated aqueous ammonium chloride solution (100 mL). The white precipitate appeared and was collected on a filter. The white solid was washed with the distilled water (3×20 mL) and dissolved in a mixture of ethyl acetate (10 mL) and methanol (10 mL). The solution was applied on a pad of silica gel and eluted with a mixture of ethyl acetate and hexane (1:1). After evaporation, 3-(4,4-dimethyl-2-oxo-1,4-dihydro-2H-benzo[d][1,3]oxazin-6-yl)-5-fluorobenzonitrile was obtained as a white solid (0.7 g, 84%): mp 253-254° C.; 1H-NMR (DMSO-d6) δ 10.4 (s, 1H, D2O exchangeable), 8.13 (s, 1H), 7.92 (m, 1H), 7.82 (m, 1H), 7.73 (m, 2H), 6.98 (d, 1H, J=8.2 Hz), 1.68 (s, 6H), 19F-NMR (DMSO-d6) δ −112.25 (m, 1F); MS (EI) m/z 296 (M+, 65%), Anal. Calc. For C17H13FN2O2: C, 68.91; H, 4.42; N, 9.45. Found: C, 68.85; H, 4.58; N, 9.14.

後処理

  1. customwas degassed
  2. customto remove oxygen
  3. temperatureThe reaction solution was cooled to room temperature
  4. additionpoured onto a cold saturated aqueous ammonium chloride solution (100 mL)
  5. customwas collected on a filter
  6. washThe white solid was washed with the distilled water (3×20 mL)
  7. dissolutiondissolved in a mixture of ethyl acetate (10 mL) and methanol (10 mL)
  8. washeluted with a mixture of ethyl acetate and hexane (1:1)
  9. customAfter evaporation

出典と根拠

ORDレコード
ord-3648184aae964d3882fec9cf2c73ba28
出典データセット
uspto-grants-2004_03
特許番号
US06713478B2

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