Dichloromethane → 2-[2-(Tert-butyl-dimethyl-silanyloxy)-ethoxy]-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-ylamine

HRID 1481554Notes

Reaction equation

HRID 1481554 reaction equation
[C:1]([Si:5]([CH3:22])([CH3:21])[O:6][CH2:7][CH2:8][O:9][C:10]1[C:15]([N+:16]([O-:18])=[O:17])=[C:14]([NH2:19])[CH:13]=[C:12](Cl)[N:11]=1)([CH3:4])([CH3:3])[CH3:2].[F:23][C:24]([F:35])([F:34])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1B(O)O.C([O-])([O-])=O.[Cs+].[Cs+].C(Cl)Cl>O1CCOCC1.CCOC(C)=O.O>[C:1]([Si:5]([CH3:22])([CH3:21])[O:6][CH2:7][CH2:8][O:9][C:10]1[C:15]([N+:16]([O-:18])=[O:17])=[C:14]([NH2:19])[CH:13]=[C:12]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=2[C:24]([F:35])([F:34])[F:23])[N:11]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 866574152-[2-(Tert-butyl-dimethyl-silanyloxy)-ethoxy]-6-chloro-3-nitro-pyridin-4-ylamine

Product 1

HCID 674124792-[2-(Tert-butyl-dimethyl-silanyloxy)-ethoxy]-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-ylamine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of 2-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-6-chloro-3-nitro-pyridin-4-ylamine (1.20 g, 3.45 mmol, prepared as described in the previous step), 2-trifluoromethyl-phenyl-boronic acid (786 mg, 4.14 mmol), Cs2CO3 (2.81 g, 8.62 mmol) and Pd(dppf)2.DCM (282 mg, 0.345 mmol) in 1,4-dioxane (12 mL) was added water (5 mL). The resulting mixture was stirred at 110° C. under microwave irradiation for 2 h and then cooled to room temperature. The resulting mixture was treated with of EtOAc (50 mL), then washed with H2O and brine and was dried (Na2SO4). Removal of the solvent under reduced pressure followed by flash chromatography of the residue on silica gel (5:95-40:60 EtOAc-hexanes) yielded 2-[2-(tert-butyl-dimethyl-silanyloxy)-ethoxy]-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-4-ylamine as a light brown solid. 1H-NMR (400 MHz, CDCl3) δ: 7.76 (d, J=7.8 Hz, 1H), 7.51-7.65 (m, 2H), 7.46 (d, J=7.3 Hz, 1H), 6.41 (s, 1H), 6.08 (br. s., 2H), 4.50 (t, J=5.3 Hz, 2H), 3.95 (t, J=5.3 Hz, 2H), 0.89 (s, 9H), 0.07 (s, 6H). Mass Spectrum (LCMS, ESI pos.) Calculated For C20H26F3N3O4Si: 458.1 (M+H). Measured: 458.0.

Workup

  1. customprepared
  2. temperaturecooled to room temperature
  3. washwashed with H2O and brine
  4. dry with materialwas dried (Na2SO4)
  5. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-90a514850d514faeac849ff86993df23
Source dataset
uspto-grants-2016_08
Patent number
US09409915B2

Reaction notes

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