Potassium Phosphate, Tribasic → methyl(E)-3-[2-fluoro-3'-(3-heptyl-1-methylureido)biphenyl-4-yl]acrylate

HRID 250836ノート

反応式

HRID 250836 の反応式
[F:1][C:2]1[CH:3]=[C:4](/[CH:16]=[CH:17]/[C:18]([O:20][CH3:21])=[O:19])[CH:5]=[CH:6][C:7]=1OS(C(F)(F)F)(=O)=O.[CH2:22]([NH:29][C:30](=[O:48])[N:31]([CH3:47])[C:32]1[CH:37]=[CH:36][CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=1)[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.[Cl-].[NH4+].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]1[CH:3]=[C:4](/[CH:16]=[CH:17]/[C:18]([O:20][CH3:21])=[O:19])[CH:5]=[CH:6][C:7]=1[C:36]1[CH:35]=[CH:34][CH:33]=[C:32]([N:31]([CH3:47])[C:30]([NH:29][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[O:48])[CH:37]=1

参加物

8

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 595749253-Heptyl-1-methyl-1-[3-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]ureaHCID 86614973methyl(E)-3-(3-fluoro-4-trifluoromethanesulfonyloxyphenyl)acrylate

生成物 1

HCID 67271925methyl(E)-3-[2-fluoro-3'-(3-heptyl-1-methylureido)biphenyl-4-yl]acrylate収率 7.3%

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 6228Dimethylformamide溶媒HCID 25517Ammonium Chloride溶媒

反応条件

温度
92.5 °C

実験手順

85 mg (0.38 mmol, 0.05 eq) of palladium acetate are added to a mixture of 2.50 g (7.6 mmol, 1 eq) of methyl (E)-3-(3-fluoro-4-trifluoromethanesulfonyloxyphenyl)acrylate, 3.71 g (9.9 mmol, 1.3 eq) of 3-heptyl-1-methyl-1-[3-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]urea (prepared as in Example 1e), 272 mg (0.78 mmol, 0.1 eq) of 2-(dicyclohexylphosphino)biphenyl and 5.5 mL of 2M potassium phosphate solution in 28 ml of dimethylformamide. The reaction mixture is heated at 90-95° C. overnight. The reaction medium is hydrolyzed in saturated ammonium chloride solution and extracted with ethyl acetate. The organic phases are combined, washed with water and dried over sodium sulfate. The solvent is evaporated off and the brown paste obtained (4.16 g) is chromatographed on silica gel (120 g CombiFlash column) eluted with 80/20 heptane/ethyl acetate. 706 mg (22%) of a “cis/trans” mixture are obtained. This solid is washed in an ethyl ether/heptane mixture, filtered and dried. 238 mg of methyl (E)-3-[2-fluoro-3′-(3-heptyl-1-methylureido)biphenyl-4-yl]acrylate in the form of a white solid are obtained. Yield=7%

後処理

  1. extractionextracted with ethyl acetate
  2. washwashed with water
  3. dry with materialdried over sodium sulfate
  4. customThe solvent is evaporated off
  5. customthe brown paste obtained (4.16 g)
  6. customis chromatographed on silica gel (120 g CombiFlash column)
  7. washeluted with 80/20 heptane/ethyl acetate
  8. custom706 mg (22%) of a “cis/trans” mixture are obtained
  9. washThis solid is washed in an ethyl ether/heptane mixture
  10. filtrationfiltered
  11. customdried

出典と根拠

ORDレコード
ord-cca1abbfdae64825a947c0fdfc547dc9
出典データセット
uspto-grants-2011_01
特許番号
US07863332B2

反応ノート

読み込み中…