Water → methyl 5-(2-(4-fluorophenyl)-3-(1H-imidazol-2-yl)-6-nitrobenzofuran-5-yl)-2-methoxybenzoate

HRID 624321Notes

Reaction equation

HRID 624321 reaction equation
FC(F)(F)S(O[C:7]1[C:8]([N+:35]([O-:37])=[O:36])=[CH:9][C:10]2[O:14][C:13]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)=[C:12]([C:22]3[N:23](S(C(F)(F)F)(=O)=O)[CH:24]=[CH:25][N:26]=3)[C:11]=2[CH:34]=1)(=O)=O.[CH3:40][O:41][C:42]1[CH:51]=[CH:50][C:49](B2OC(C)(C)C(C)(C)O2)=[CH:48][C:43]=1[C:44]([O:46][CH3:47])=[O:45].P([O-])([O-])([O-])=O.[K+].[K+].[K+].O>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[F:21][C:18]1[CH:17]=[CH:16][C:15]([C:13]2[O:14][C:10]3[CH:9]=[C:8]([N+:35]([O-:37])=[O:36])[C:7]([C:49]4[CH:50]=[CH:51][C:42]([O:41][CH3:40])=[C:43]([CH:48]=4)[C:44]([O:46][CH3:47])=[O:45])=[CH:34][C:11]=3[C:12]=2[C:22]2[NH:26][CH:25]=[CH:24][N:23]=2)=[CH:20][CH:19]=1

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 22930502Methyl 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 866916312-(4-fluorophenyl)-6-nitro-3-(1-((trifluoromethyl)sulfonyl)-1H-imidazol-2-yl)benzofuran-5-yl trifluoromethanesulfonate

Product 1

HCID 86691630methyl 5-(2-(4-fluorophenyl)-3-(1H-imidazol-2-yl)-6-nitrobenzofuran-5-yl)-2-methoxybenzoate

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-(4-fluorophenyl)-6-nitro-3-(1-((trifluoromethyl)sulfonyl)-1H-imidazol-2-yl)benzofuran-5-yl trifluoromethanesulfonate (500 mg, 0.829 mmol), methyl 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (290 mg, 0.994 mmol), potassium phosphate (352 mg, 1.657 mmol) in a mixture of dioxane (40 mL)/water (4 mL) in a pressure tube at rt was degassed, and then added with PdCl2(dppf)-CH2Cl2 adduct (67.7 mg, 0.083 mmol). The reaction mixture was heated to 100° C. and maintained at the same temperature overnight. The reaction mixture was filtered through celite, and the celite bed washed with EtOAc. The filtrate was concentrated, and the residue was purified by Combiflash using a mixture of petroleum ether and EtOAc as an eluant and a 40 g silica column. The title compound was collected at 70% EtOAc in pet. ether. Yield: 375 mg (93%). 1H NMR (400 MHz, DMSO-d6) δ ppm: 12.52 (br s, 1H) 8.52 (s, 1H) 8.10-8.20 (m, 1H) 7.58-7.82 (m, 2H) 7.56 (dd, J=8.53, 2.51 Hz, 1H) 7.36-7.47 (m, 4H) 7.18-7.32 (m, 2H) 3.89 (s, 3H) 3.80 (s, 3H); LCMS: (ES−) m/z=486.0 (M−H); Column—Acentis Express C8 (50×2.1 mm; 2.7 u); M phase A: 10 mM Ammonium Formate in Water:MeCN (90:10); M phase B: 10 mM Ammonium Formate in Water:MeCN (10:90)

Workup

  1. customwas degassed
  2. temperaturemaintained at the same temperature overnight
  3. filtrationThe reaction mixture was filtered through celite
  4. washthe celite bed washed with EtOAc
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified by Combiflash
  7. additiona mixture of petroleum ether and EtOAc as an eluant
  8. customThe title compound was collected at 70% EtOAc in pet. ether

Sources & evidence

ORD record
ord-940e53fb0fb5479f9a5535e71ef2c55a
Source dataset
uspto-grants-2016_04
Patent number
US09303020B2

Reaction notes

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