Hydrochloric Acid → 5-Fluoro-2-(6-hydroxy-2-naphthyl)benzamide

HRID 735373

反応式

HRID 735373 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([OH:12])[CH:6]=[CH:5]2.[F:13][C:14]1[CH:15]=[CH:16][C:17](B2OC(C)(C)C(C)(C)O2)=[C:18]([CH:21]=1)[C:19]#[N:20].C(=O)([O-])[O-:32].[Na+].[Na+].Cl>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:13][C:14]1[CH:15]=[CH:16][C:17]([C:2]2[CH:11]=[CH:10][C:9]3[C:4](=[CH:5][CH:6]=[C:7]([OH:12])[CH:8]=3)[CH:3]=2)=[C:18]([CH:21]=1)[C:19]([NH2:20])=[O:32]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 271446-Bromo-2-naphthalenolHCID 221807905-Fluoro-2-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile

生成物 1

HCID 689016405-Fluoro-2-(6-hydroxy-2-naphthyl)benzamide

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

A mixture of 6-bromo-2-naphthol (12.0 g, 52.2 mmol), 5-fluoro-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzonitrile (16.7 g, 67.6 mmol, prepared according to the method disclosed in patent WO/2003099816), sodium carbonate solution (2M, 75 mL) and tetrakis(triphenylphosphine)palladium (0) (1.2 g, 1.0 mmol) in 1,4-dioxane (360 mL) was heated at 80° C. for 17 hours. It was allowed to cool then poured into dilute hydrochloric acid (1 M, 360 mL) and extracted with ethyl acetate (3×200 mL). These extracts were washed with water and brine then dried (MgSO4), filtered and the solution concentrated in vacuo to a volume of ˜100 mL. Solid was filtered off and sucked dry to give 5-fluoro-2-(6-hydroxy-2-naphthyl)benzamide as a white solid. This solid (6.3 g, 22.4 mmol) was suspended in dichloromethane (130 mL)/pyridine (11 mL) at 0° C. under nitrogen, and trifluoromethane sulfonic anhydride (11 mL, 65.5 mmol) added gradually over 40 minutes before leaving overnight to return to ambient temperature. Solvent was removed in vacuo, water (400 mL) added and extracted into ethyl acetate (2×300 mL). These extracts were washed with water and brine then dried (MgSO4), filtered and solvent removed in vacuo. Purification by flash column chromatography eluting with 10% ethyl acetate/isohexane gave 6-(2-cyano-4-fluorophenyl)-2-naphthyl trifluoromethanesulfonate (8.0 g, 38%). 1H NMR (500 MHz, CDCl3) δ 8.06 (1H, s), 8.01 (2H, dd, J=4.0, 9.0 Hz), 7.82 (1H, d, J=2.3 Hz), 7.73 (1H, dd, J=1.7, 8.5 Hz), 7.60 (1H, dd, J=5.2, 8.6 Hz), 7.53 (1H, dd, J=2.6, 7.9 Hz), 7.47-7.41 (2H, m).

後処理

  1. customprepared
  2. temperatureto cool
  3. extractionextracted with ethyl acetate (3×200 mL)
  4. washThese extracts were washed with water and brine
  5. dry with materialthen dried (MgSO4)
  6. filtrationfiltered
  7. concentrationthe solution concentrated in vacuo to a volume of ˜100 mL
  8. filtrationSolid was filtered off
  9. customsucked dry

出典と根拠

ORDレコード
ord-b27f5cf0ae4b43beb311cacc04c5ebbd
出典データセット
uspto-grants-2009_09
特許番号
US07592456B2

関連ノート

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