Water → (E)-methyl 3-(2-methyl-5-(1-methyl-1H-indazol-5-yl)-4-(4-(trifluoromethyl)styryl)phenyl)propanoate

HRID 1620033Notes

Reaction equation

HRID 1620033 reaction equation
F[B-](F)(F)F.[CH3:6][O:7][C:8]([CH2:10][CH2:11][C:12]1[C:17]([CH3:18])=[CH:16][C:15]([N+]#N)=[C:14]([C:21]2[CH:22]=[C:23]3[C:27](=[CH:28][CH:29]=2)[N:26]([CH3:30])[N:25]=[CH:24]3)[CH:13]=1)=[O:9].O.[F:32][C:33]([F:46])([F:45])[C:34]1[CH:44]=[CH:43][C:37](/[CH:38]=[CH:39]/B(O)O)=[CH:36][CH:35]=1.C(=O)([O-])O.[Na+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2].C(OCC)(=O)C>[CH3:18][C:17]1[CH:16]=[C:15](/[CH:39]=[CH:38]/[C:37]2[CH:36]=[CH:35][C:34]([C:33]([F:32])([F:45])[F:46])=[CH:44][CH:43]=2)[C:14]([C:21]2[CH:22]=[C:23]3[C:27](=[CH:28][CH:29]=2)[N:26]([CH3:30])[N:25]=[CH:24]3)=[CH:13][C:12]=1[CH2:11][CH2:10][C:8]([O:7][CH3:6])=[O:9]

Participants

8

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 6153620trans-2-[4-(Trifluoromethyl)phenyl]vinylboronic acidHCID 866408694-(2-methoxycarbonylethyl)-5-methyl-2-(1-methyl-1H-indazol-5-yl)benzenediazonium tetrafluoroborate

Product 1

HCID 66876711(E)-methyl 3-(2-methyl-5-(1-methyl-1H-indazol-5-yl)-4-(4-(trifluoromethyl)styryl)phenyl)propanoateYield 13.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Example Compound 2-N1-1 (324 mg) was dissolved in a 50% aqueous solution of HBF4 (0.5 ml), and this solution was added dropwise with an aqueous solution (0.5 ml) of sodium nitrite (83 mg) under ice cooling. The reaction mixture was stirred for 30 minutes, and then the precipitates were collected by filtration to obtain 4-(2-methoxycarbonylethyl)-5-methyl-2-(1-methyl-1H-indazol-5-yl)benzenediazonium tetrafluoroborate (Intermediate 16, yield: 200 mg). A solution of this Intermediate 16 (200 mg) in 1,4-dioxane (1 ml) was successively added with water (1 ml), (E)-4-(trifluoromethyl)styrylboronic acid (200 mg, Ald), and Pd(OAc)2 (20 mg, Ald), and stirred at room temperature for 3 hours. The reaction mixture was added with saturated aqueous sodium hydrogencarbonate (15 ml) and ethyl acetate to extract the organic layer, and washed with saturated brine (30 ml), and then solvent was evaporated. The residue was purified by silica gel column chromatography (Yamazen, n-hexane:ethyl acetate=3:1) to obtain the title compound (30 mg).

Workup

  1. extractionto extract the organic layer
  2. washwashed with saturated brine (30 ml)
  3. customsolvent was evaporated
  4. customThe residue was purified by silica gel column chromatography (Yamazen, n-hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-19c79ff77a714f389bc4690477299226
Source dataset
uspto-grants-2014_07
Patent number
US08772327B2

Reaction notes

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