Ammonium Chloride → HCID 66764449, compound

HRID 1400061Notes

Reaction equation

HRID 1400061 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[CH2:12][C:13]#[N:14].[CH2:15]([Si:17]([CH2:22][CH3:23])([CH2:20][CH3:21])[C:18]#[CH:19])[CH3:16].[NH4+].[Cl-]>N(C(C)C)C(C)C.CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:18]([Si:17]([C:15]#[C:16][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[CH2:12][C:13]#[N:14])([CH2:22][CH3:23])[CH2:20][CH3:21])[CH3:19]

Participants

9

Reactant 3

HCID 25517Ammonium ChlorideHCID 637947(Triethylsilyl)acetyleneHCID 27784362-Bromo-4-(trifluoromethyl)phenylacetonitrile

Product 1

HCID 66764449HCID 66764449, compoundYield 99.7%

Reagents, catalysts & solvents 5

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 7912DiisopropylamineSolvent

Procedure

Bis(triphenylphosphine)palladium(II) chloride (0.106 g, 0.151 mmol), copper(I) iodide (0.058 g, 0.303 mmol) and triphenylphospine (0.079 g, 0.303 mmol) are dissolved in a mixture of i-Pr2NH (11.36 ml)/DMF (3.79 ml) (degassed with N2 for 15 min). 2-(2-Bromo-4-(trifluoromethyl)phenyl)acetonitrile (1.1 g, 3.8 mmol) is added to the resultant orange solution. The mixture is stirred at RT for one hour. Triethyl(ethynyl)silane (1.018 ml, 5.68 mmol) is added dropwise, and the batch is warmed to 80° C. After 1 hour, a saturated, aqueous NH4Cl solution (50 ml) is added to the strongly dark-coloured batch. After phase separation, the aqueous phase is extracted three times with 50 ml of ethyl acetate each time. The combined organic phases are dried over Na2SO4 and evaporated to dryness in vacuo. The residue is purified by chromatography on silica gel with a 98:2 mixture of petroleum ether and ethyl acetate, giving 2-(2-((triethylsilyl)ethynyl)-4-(trifluoromethyl)phenyl)acetonitrile (orange oil, 91%, 1.226 g, 3.79 mmol);

Workup

  1. temperaturethe batch is warmed to 80° C
  2. waitAfter 1 hour
  3. customAfter phase separation
  4. extractionthe aqueous phase is extracted three times with 50 ml of ethyl acetate each time
  5. dry with materialThe combined organic phases are dried over Na2SO4
  6. customevaporated to dryness in vacuo
  7. customThe residue is purified by chromatography on silica gel with a 98:2 mixture of petroleum ether and ethyl acetate

Sources & evidence

ORD record
ord-9d91c57eb0e245aeab28cccf9fd41eb7
Source dataset
uspto-grants-2014_12
Patent number
US08906916B2

Reaction notes

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