Dimethylformamide → HCID 59199440, compound

HRID 2089538Notes

Reaction equation

HRID 2089538 reaction equation
[CH:1]([O:4][C:5]([C:7]1[N:8]([CH:12]2[C:21]3[C:16](=[CH:17][C:18](OS(C(F)(F)F)(=O)=O)=[CH:19][CH:20]=3)[CH2:15][CH2:14][CH2:13]2)[CH:9]=[N:10][CH:11]=1)=[O:6])([CH3:3])[CH3:2].[F:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.C(=O)([O-])[O-].[Na+].[Na+].CN(C=O)C>O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:1]([O:4][C:5]([C:7]1[N:8]([CH:12]2[C:21]3[C:16](=[CH:17][C:18]([C:34]4[CH:35]=[CH:36][C:31]([F:30])=[CH:32][CH:33]=4)=[CH:19][CH:20]=3)[CH2:15][CH2:14][CH2:13]2)[CH:9]=[N:10][CH:11]=1)=[O:6])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 59199400HCID 59199400, compound

Product 1

HCID 59199440HCID 59199440, compound

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A flask is charged with 3-(6-trifluoromethanesulfonyloxy-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester (0.225 g, 0.520 mmol), 4-fluorophenylboronic acid (0.145 g, 1.041 mmol), aqueous sodium carbonate (2M, 1.30 mL, 2.60 mmol) and DMF (35 mL). Tetrakis(triphenylphosphine) palladium (0.060 g, 0.052 mmol) is added and the mixture is heated to 150° C. in a sealed tube under microwave irradiation conditions for 12 minutes. The reaction is cooled to room temperature, diluted with water and extracted with dichloromethane. The organic phase is dried with Na2SO4, filtered, and concentrated to give a residue, which is purified by silica gel chromatography (hexanes-ethyl acetate mixtures) to give 3-[6-(4-fluoro-phenyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-3H-imidazole-4-carboxylic acid isopropyl ester. MS: (ESI) m/z 379.2 (M+H)+. The HCl salt of the title compound can be prepared by dissolution in diethyl ether followed by treatment with an excess of 1N HCl in diethyl ether. The resulting heterogeneous solution is concentrated to furnish the HCl salt of 3-[6-(4-fluoro-phenyl)-1,2,3,4-tetrahydro-naphthalen-1-yl]-3H-imidazole-4-carboxylic acid isopropyl ester; 1H NMR (400 MHz, MeOD) δ ppm 1.45 (d, J=6.3 Hz, 3 H), 1.47 (d, J=6.3 Hz, 3 H), 1.75-1.86 (m, 1 H), 1.93-2.02 (m, 1 H), 2.31-2.47 (m, 2 H), 2.99 (ddd, J=17.0, 9.3, 5.6 Hz, 1 H), 3.13 (dt, J=17.0, 5.3 Hz, 1 H), 5.36 (sept, J=6.3 Hz, 1 H), 6.61 (t, J=5.1 Hz, 1 H), 7.19-7.25 (m, 3 H), 7.51 (dd, J=8.1, 2.0 Hz, 1 H), 7.57 (s, 1 H), 7.66-7.72 (m, 2 H), 8.34 (d, J=1.5 Hz, 1 H), 8.65 (d, J=1.3 Hz, 1 H).

Workup

  1. temperatureThe reaction is cooled to room temperature
  2. extractionextracted with dichloromethane
  3. dry with materialThe organic phase is dried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a residue, which
  7. customis purified by silica gel chromatography (hexanes-ethyl acetate mixtures)

Sources & evidence

ORD record
ord-c378eb5c5cc84373a3e1a8789e6abfdd
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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