Cesium carbonate → Methyl 4-[3'-fluoro-4'-(formylamino)-1,1'-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoate

HRID 907694

反応式

HRID 907694 の反応式
[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]

参加物

10

反応物 5

HCID 10796Cesium carbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 21985797Methyl 4-(4-bromophenyl)-2,2-dimethyl-4-oxobutanoateHCID 23549341N-(2-fluoro-4-iodophenyl)formamide

生成物 1

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

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

実験手順

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 (MHz; 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).

後処理

  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)

出典と根拠

ORDレコード
ord-9dc9249a0a464907995d82afbb9dde70
出典データセット
uspto-grants-2011_09
特許番号
US08013166B2

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