Sodium Carbonate → 2-(2-Chloro-5-methylpyrimidin-4-yl)benzo[b]thiophen-4-ol

HRID 1986245ノート

反応式

HRID 1986245 の反応式
[S:1]1[CH:5]=[CH:4][C:3]2[C:6]([O:10][Si](C(C)(C)C)(C)C)=[CH:7][CH:8]=[CH:9][C:2]1=2.C(OB(OC(C)C)OC(C)C)(C)C.C([N-]C(C)C)(C)C.[Li+].[Cl:39][C:40]1[N:45]=[C:44](Cl)[C:43]([CH3:47])=[CH:42][N:41]=1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.CCCCCCC.C1COCC1.C(C1C=CC=CC=1)C.ClCCl.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].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:39][C:40]1[N:45]=[C:44]([C:5]2[S:1][C:2]3[CH:9]=[CH:8][CH:7]=[C:6]([OH:10])[C:3]=3[CH:4]=2)[C:43]([CH3:47])=[CH:42][N:41]=1

参加物

11

反応物 5

HCID 10340Sodium CarbonateHCID 21531Triisopropyl borateHCID 74508Pyrimidine, 2,4-dichloro-5-methyl-HCID 2724682Lithium diisopropylamideHCID 68856170(Benzo[b]thiophen-4-yloxy)(tert-butyl)dimethylsilane

生成物 1

HCID 1363439692-(2-Chloro-5-methylpyrimidin-4-yl)benzo[b]thiophen-4-ol収率 16.8%

試薬・触媒・溶媒 5

HCID 167845palladium(II) acetate触媒HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒HCID 22742125Tetrahydrofuran heptane ethylbenzol溶媒

反応条件

温度
-70 °C

実験手順

To a −65° C. solution of (benzo[b]thiophen-4-yloxy)(tert-butyl)dimethylsilane (6.25 g, 23.6 mmol) and triisopropylborate (4.89 g, 26.0 mmol) in THF (60 mL) is added lithium diisopropylamide (13.0 mL of a 2 M solution in heptane/THF/ethylbenzene, 26.0 mmol) dropwise over 5 minutes. The mixture is stirred for 2 hours at −70° C., whereupon the cold bath is removed and the mixture is allowed to warm to room temperature. After 2 hours, to the mixture is then added 2,4-dichloro-5-methylpyrimidine (3.85 g, 23.6 mmol), 2M Na2CO3 (23.6 mL, 47.2 mmol), 1,1′-bis(diphenylphosphino) ferrocene (655 mg, 1.18 mmol) and palladium(II) acetate (265 mg, 1.18 mmol) and the mixture is heated to reflux for 18 hours. Upon cooling to room temperature, the mixture is concentrated under reduced pressure, extracted from water (100 mL) with dichloromethane (3×150 mL) and the organic extracts are concentrated under reduced pressure. The crude material is subjected to chromatography on silica gel, eluting with dichloromethane in hexanes 50-100%, followed by CHCl3 in MeOH 0-100%, to obtain a dark solid. The crude material is extracted from 1 N NaOH (125 mL) with dichloromethane (3×100 mL). The aqueous layer is acidified with 5 N HCl, exhaustively extracted with 10% CHCl3/MeOH followed by 1:1 THF/dichloromethane and concentrated to yield a dark solid. Sonication of the solid in dichloromethane and filtration yielded the title compound as a brown solid (1.10 g, 12% yield).

後処理

  1. customis removed
  2. temperatureto warm to room temperature
  3. waitAfter 2 hours
  4. temperatureto reflux for 18 hours
  5. temperatureUpon cooling to room temperature
  6. concentrationthe mixture is concentrated under reduced pressure
  7. extractionextracted from water (100 mL) with dichloromethane (3×150 mL)
  8. concentrationthe organic extracts are concentrated under reduced pressure
  9. washeluting with dichloromethane in hexanes 50-100%
  10. customto obtain a dark solid
  11. extractionThe crude material is extracted from 1 N NaOH (125 mL) with dichloromethane (3×100 mL)
  12. extractionexhaustively extracted with 10% CHCl3/MeOH
  13. concentrationconcentrated
  14. customto yield a dark solid
  15. filtrationfiltration

出典と根拠

ORDレコード
ord-7f6f18166168476f992db4e5ed633239
出典データセット
uspto-grants-2009_06
特許番号
US07547691B2

反応ノート

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