Hydrochloric Acid → HCID 53237072, compound

HRID 1897610Notes

Reaction equation

HRID 1897610 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8](B2OC(C)(C)C(C)(C)O2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].Br[C:20]1[CH:21]=[N:22][CH:23]=[C:24]([F:37])[C:25]=1[CH:26]([OH:36])[CH2:27][O:28][Si](C(C)(C)C)(C)C.C(=O)([O-])[O-].[Na+].[Na+].C(Cl)Cl.Cl.O1CCOCC1>C(OCC)(=O)C.CN(C=O)C>[Cl:1][C:2]1[CH:9]=[C:8]([C:20]2[CH:21]=[N:22][CH:23]=[C:24]([F:37])[C:25]=2[CH:26]([OH:36])[CH2:27][OH:28])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 579261132-Chloro-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrileHCID 71087244HCID 71087244, compound

Product 1

HCID 53237072HCID 53237072, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A 25 mL round bottom flask was charged with 2-chloro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzonitrile (250 mg, 0.949 mmol), 1-(3-bromo-5-fluoro-pyridin-4-yl)-2-(tert-butyl-dimethyl-silanyloxy)-ethanol (332 mg, 0.949 mmol), 2M aqueous sodium carbonate (0.95 mL, 1.90 mmol) and DMF (5 mL). The reaction mixture was evacuated and flushed with N2 twice followed by addition of PdCl2(dppf).CH2Cl2 adduct (38.7 mg, 0.047 mmol). The reaction was stirred under N2 at 100° C. for 3 days. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and washed with water twice. The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude was dissolved in DMF (5 mL) and 4M HCl solution in dioxane (2.372 mL, 9.49 mmol). The reaction mixture was stirred at room temperature for 1 hr. The reaction mixture was quenched with saturated NaHCO3 solution and extracted with DCM twice. The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude was purified by silica gel flash chromatography employing DCM-MeOH (9:1) to afford 2-chloro-4-[4-(1,2-dihydroxy-ethyl)-5-fluoro-pyridin-3-yl]-benzonitrile. 1H NMR (400 MHz, MeOD) δ ppm 3.72-4.03 (m, 1H), 4.80 (t, J=6.8 Hz, 1H), 7.61 (dd, J=8.0, 1.6 Hz, 1H), 7.82 (d, J=1.3 Hz, 1H), 7.95 (d, J=8.1 Hz, 1H), 8.31 (s, 1H), 8.55 (d, J=2.5 Hz, 1H); HRMS: (ESI) ink 293.0488 [(M+H)+ Calcd for C14H10ClFN2O2 293.0493].

Workup

  1. customThe reaction mixture was evacuated
  2. customflushed with N2
  3. additiontwice followed by addition of PdCl2(dppf)
  4. temperatureThe reaction mixture was cooled to room temperature
  5. washwashed with water twice
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. dissolutionThe crude was dissolved in DMF (5 mL)
  9. stirringThe reaction mixture was stirred at room temperature for 1 hr
  10. customThe reaction mixture was quenched with saturated NaHCO3 solution
  11. extractionextracted with DCM twice
  12. dry with materialThe organic layer was dried over sodium sulfate
  13. concentrationconcentrated in vacuo
  14. customThe crude was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-450c2ce6547a458e8ce83a296bea3df0
Source dataset
uspto-grants-2013_08
Patent number
US08519134B2

Reaction notes

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