Dimethylcarbamoyl Chloride → 6-(4-Chloro-phenyl)-5-cyclopropylmethoxy-pyridine-2-carbonitrile

HRID 1528373Notes

Reaction equation

HRID 1528373 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([O:14][CH2:15][CH:16]3[CH2:18][CH2:17]3)=[CH:12][CH:11]=[CH:10][N+:9]=2[O-])=[CH:4][CH:3]=1.[CH2:20]([N:22](CC)CC)C.CN(C)C(Cl)=O.C[Si](C#N)(C)C>C(#N)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([C:20]#[N:22])[CH:11]=[CH:12][C:13]=2[O:14][CH2:15][CH:16]2[CH2:18][CH2:17]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6598Dimethylcarbamoyl ChlorideHCID 8471TriethylamineHCID 82115Trimethylsilyl cyanideHCID 666786042-(4-Chloro-phenyl)-3-cyclopropylmethoxy-pyridine 1-oxide

Product 1

HCID 666786996-(4-Chloro-phenyl)-5-cyclopropylmethoxy-pyridine-2-carbonitrileYield 59.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 25 g 2-(4-chloro-phenyl)-3-cyclopropylmethoxy-pyridine 1-oxide in 500 mL acetonitrile, 9.23 g triethylamine and 10.73 g dimethylcarbamoylchlorid were added. After 5 minutes at room temperature, 27.88 g trimethylsilylcyanid was added. The reaction mixture was stirred at 90° C. over 15 h. The reaction mixture was partitioned between water and ethyl acetate; then extracted. The organic phase was washed with brine; then dried over MgSO4 and purified by chromatography on silica gel with a gradient of heptane to heptane:ethyl acetate 2:1 to yield 15.30 g (59.26%) of the title compound as light yellow solid, MS 285.1 (M+H)+.

Workup

  1. customThe reaction mixture was partitioned between water and ethyl acetate
  2. extractionthen extracted
  3. washThe organic phase was washed with brine
  4. dry with materialthen dried over MgSO4
  5. custompurified by chromatography on silica gel with a gradient of heptane to heptane:ethyl acetate 2:1

Sources & evidence

ORD record
ord-e453291991294a24a66c3827673e2be1
Source dataset
uspto-grants-2015_07
Patent number
US09090599B2

Reaction notes

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