碳酸氢铯 → Methyl 4-[3'-fluoro-4'-(formylamino)-1,1'-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoate

HRID 9554

反应方程式

HRID 9554 反应方程式
[F:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][C:3]=1[NH:9][CH:10]=[O:11].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:36]1[CH:41]=[CH:40][C:39]([C:42](=[O:51])[CH2:43][C:44]([CH3:50])([CH3:49])[C:45]([O:47][CH3:48])=[O:46])=[CH:38][CH:37]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.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.O>[F:1][C:2]1[CH:7]=[C:6]([C:36]2[CH:37]=[CH:38][C:39]([C:42](=[O:51])[CH2:43][C:44]([CH3:49])([CH3:50])[C:45]([O:47][CH3:48])=[O:46])=[CH:40][CH:41]=2)[CH:5]=[CH:4][C:3]=1[NH:9][CH:10]=[O:11]

参与物

10

反应物 5

HCID 10796碳酸氢铯HCID 517044乙酸钾HCID 2733548联硼酸频那醇酯HCID 21985797Methyl 4-(4-bromophenyl)-2,2-dimethyl-4-oxobutanoateHCID 23549341N-(2-fluoro-4-iodophenyl)formamide

产物 1

HCID 21985807Methyl 4-[3'-fluoro-4'-(formylamino)-1,1'-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoate收率 46%

试剂、催化剂与溶剂 4

HCID 167845palladium acetate催化剂HCID 178418397HCID 178418397，化合物催化剂HCID 962聚[6-[4-(4-氰基苯基)苯氧基]己基甲基丙烯酸酯]溶剂HCID 6228N,N-二甲基甲酰胺溶剂

反应条件

温度
80 °C

实验过程

A suspension of 2-fluoro-4-iodophenylformamide (1.94 g, 7.35 mmol, prepared as described above), bis(pinacolato)diboron (1.86 g, 7.35 mmol), potassium acetate (2.16 g, 22.1 mmol), and palladium acetate (49.4 mg, 0.22 mmol) in N,N-dimethylformamide (50 mL) was degassed by bubbling a flow of argon through the mixture for 30 minutes. The mixture was then heated at 80° C. for 3 h. After the mixture was cooled to rt, methyl 4-(4-bromophenyl)-2,2-dimethyl-4-oxobutanoate (2.2 g, 7.4 mmol), tetrakis(triphenylphosphine)palladium(0) (254.8 mg, 0.22 mmol), and cesium carbonate (3.59 g, 11.0 mmol) were added, and the reaction mixture was heated at 80° C. for 16 h. The mixture was then cooled to rt and water was added. The mixture was extracted with ethyl acetate and the combined extracts were dried over sodium sulfate. The mixture was concentrated under reduced pressure and the crude was purified by flash chromatography (Biotage Flash 40M, 1:1 ethyl acetate/hexane) to afford methyl 4-[3′-fluoro-4′-(formylamino)-1,1′-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoate (1.2 g, 46%). LC-MS ret. time 2.80 min, m/z 358.1 (MH+); 1H NMR (300 MHz, DMSO-d6) δ 1.19 (s, 6H), 3.36 (s, 2H), 3.51 (s, 3H), 7.56 (d, 1H), 7.69 (dd, 1H), 7.82 (d, 2H), 7.99 (d, 3H), 8.21 (t), 10.25 (s, 1H).

后处理

  1. customwas degassed
  2. customby bubbling a flow of argon through the mixture for 30 minutes
  3. temperatureAfter the mixture was cooled to rt
  4. temperaturethe reaction mixture was heated at 80° C. for 16 h
  5. temperatureThe mixture was then cooled to rt
  6. extractionThe mixture was extracted with ethyl acetate
  7. dry with materialthe combined extracts were dried over sodium sulfate
  8. concentrationThe mixture was concentrated under reduced pressure
  9. customthe crude was purified by flash chromatography (Biotage Flash 40M, 1:1 ethyl acetate/hexane)

来源与证据

ORD记录
ord-2cdaf61949d6482f90619953faff2a79
来源数据集
uspto-grants-2006_08
专利号
US07091228B2

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