Ether, bis(1-chloroethyl) → 6-Chloro-5-methoxymethoxy-nicotinonitrile

HRID 1255724

Reaction equation

HRID 1255724 reaction equation
[Cl:1][C:2]1[C:9]([OH:10])=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=1.C(N(CC)C(C)C)(C)C.Cl[CH:21]([O:23][CH:24](C)Cl)C>C(Cl)Cl>[Cl:1][C:2]1[C:9]([O:10][CH2:21][O:23][CH3:24])=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 23419Ether, bis(1-chloroethyl)HCID 81531DiisopropylethylamineHCID 866364556-Chloro-5-hydroxynicotinonitrile

Product 1

HCID 866364566-Chloro-5-methoxymethoxy-nicotinonitrileYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 6-chloro-5-hydroxy-nicotinonitrile (1.12 g, 7.24 mmol) in DCM (15 mL) was added N,N-diisopropyl ethylamine (1.57 mL, 9.05 mmol) followed by the addition of chloro-methyl methylether (0.66 mL, 8.69 mmol) slowly at 0° C. After overnight at room temperature, the reaction mixture was washed with saturated NaHCO3 (10 mL) and brine (10 mL), dried over Na2SO4, filtered, and concentrated to give yellow oil. Purification was accomplished by flash chromatography on silica gel using 5-25% EtOAc/hexanes gradient elution to yield the title compound (0.68 g, 50%) as a transparent oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.53 (d, J=2.0 Hz, 1H), 8.14 (d, J=2.0 Hz, 1H), 5.42 (s, 2H), 3.40 (s, 3H); MS (ES) m/z: 199 (M+1)+.

Workup

  1. washthe reaction mixture was washed with saturated NaHCO3 (10 mL) and brine (10 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give yellow oil
  6. customPurification
  7. washwas accomplished by flash chromatography on silica gel using 5-25% EtOAc/hexanes gradient elution

Sources & evidence

ORD record
ord-f4eaa73db0044aca82457de5d20288fe
Source dataset
uspto-grants-2013_06
Patent number
US08461135B2

Linked notes

Loading…