Ammonium Chloride → HCID 90043538, compound

HRID 1479936Notes

Reaction equation

HRID 1479936 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5](F)=[N:6][CH:7]=1.[CH:9]1([C:12]#[N:13])[CH2:11][CH2:10]1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[NH4+].[Cl-]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:9]2([C:12]#[N:13])[CH2:11][CH2:10]2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 79637CyclopropanecarbonitrileHCID 3458175-Chloro-2-fluoropyridineHCID 3251421Potassium bis(trimethylsilyl)amide

Product 1

HCID 90043538HCID 90043538, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
22 °C

Procedure

To a solution of 5-chloro-2-fluoropyridine (2 g, 1.53 ml, 15.2 mmol, Eq: 1.00) and cyclopropanecarbonitrile (1.02 g, 1.15 ml, 15.2 mmol, Eq: 1.00) in toluene (20.0 ml) was added dropwise over 5 min. KHMDS 0.5 M in toluene (30.4 ml, 15.2 mmol, Eq: 1.00) at 0° C. The solution turned brown. After 45 min, the reaction mixture was allowed to warm up to 22° C. and stirred for 2.5 h. Saturated aqueous NH4Cl solution (50 ml) was then added and the aqueous phase was extracted with AcOEt (3×60 ml). The combined organic phases were dried over Na2SO4, filtered and concertrated under reduced pressure. The crude material was purified by flash chromatography (silica gel, 70 g, 0% to 20% EtOAc in heptane) to yield the title compound as a white solid (840 mg; 31%). m/z=179.0373 [M+H]+.

Workup

  1. customat 0° C
  2. extractionthe aqueous phase was extracted with AcOEt (3×60 ml)
  3. dry with materialThe combined organic phases were dried over Na2SO4
  4. filtrationfiltered
  5. customThe crude material was purified by flash chromatography (silica gel, 70 g, 0% to 20% EtOAc in heptane)

Sources & evidence

ORD record
ord-e1062b4a0cc14db7b428daadc73809b6
Source dataset
uspto-grants-2016_08
Patent number
US09409882B2

Reaction notes

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