Imidazole → HCID 86730058, compound

HRID 595037Notes

Reaction equation

HRID 595037 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][OH:9])=[CH:4][CH:3]=1.[C:10]([Si:14](Cl)([CH3:16])[CH3:15])([CH3:13])([CH3:12])[CH3:11].N1C=CN=C1.C(O)(C(F)(F)F)=O>CN(C=O)C.CCOCC.O.CO>[Si:14]([O:9][CH2:8][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[N:7][CH:6]=1)([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:16])[CH3:15]

Participants

8

Reactant 4

HCID 795ImidazoleHCID 6422Trifluoroacetic acidHCID 28928tert-Butyldimethylsilyl chlorideHCID 177161(6-Chloropyridin-3-yl)methanol

Product 1

HCID 86730058HCID 86730058, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 22242641Methanol--water (1/1)Solvent

Procedure

To a stirred solution of (6-chloropyridin-3-yl)methanol (643 mg, 4.48 mmol) in DMF (15 mL) was added tert-butylchlorodimethylsilane (675 mg, 4.48 mmol) and imidazole (610 mg, 8.96 mmol). The reaction mixture was stirred at room temperature for 5 h, then diluted with 200 mL of ether, washed with saturated NaHCO3 solution, 10% LiCl solution, and brine. The solution was dried with anhydrous MgSO4, filtered and concentrated. The residue was purified by silica gel chromatography (hexane/EtOAc) to provide Preparation 47A (869 mg, 75%). HPLC: RT=3.623 min (H2O/MeOH with TFA, CHROMOLITH® ODS, 4.6×50 mm, gradient=4 min, wavelength=220 nm); MS(ES): m/z=258 [M+H+]; 1H NMR (400 MHz, DMSO-d6) δ 8.35 (d, J=1.8 Hz, 1H), 7.77 (dd, J=8.1, 2.4 Hz, 1H), 7.50 (d, J=8.4 Hz, 1H), 4.75 (s, 2H), 0.93-0.86 (m, 9H), 0.12-0.06 (m, 6H).

Workup

  1. washwashed with saturated NaHCO3 solution, 10% LiCl solution, and brine
  2. dry with materialThe solution was dried with anhydrous MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography (hexane/EtOAc)
  6. customto provide

Sources & evidence

ORD record
ord-071ad802d2024687b4c8afb9cba77495
Source dataset
uspto-grants-2016_01
Patent number
US09242941B2

Reaction notes

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