Diisopropylamine → Methyl 2-((trimethylsilyl)ethynyl)isonicotinate

HRID 2064256Notes

Reaction equation

HRID 2064256 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[C:12]([Si:14]([CH3:17])([CH3:16])[CH3:15])#[CH:13].C(NC(C)C)(C)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)I.C(#N)C>[CH3:15][Si:14]([C:12]#[C:13][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6])([CH3:17])[CH3:16]

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 66111TrimethylsilylacetyleneHCID 38477682-Bromo-isonicotinic acid methyl ester

Product 1

HCID 67151190Methyl 2-((trimethylsilyl)ethynyl)isonicotinateYield 82%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalyst2×HCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
10 °C

Procedure

Methyl 2-bromoisonicotinate (216 g, 1 mol), dry acetonitrile (1.7 L), ethynyl(trimethyl)silane (117 g, 1.2 mol), diisopropylamine (122 g, 1.2 mol), and dichlorobis(triphenylphosphine)palladium (36 g, 0.05 mol) were placed into a well dried three necked flask which was twice purged with a stream of nitrogen. The reaction mixture was stirred for 0.5 hours, cooled to 10° C., and copper iodide (19 g, 0.1 mol) was added under a stream of nitrogen. At 20° C., the reaction mixture became thick and black and an exotherm was observed which was followed by formation of a precipitate. After the addition of copper iodide, the reaction mixture was stirred for further 2 hours at ambient temperature. The precipitated residue was separated by filtration and twice washed with diethyl ether (800 mL). The filtrate was washed with saturated ammonium chloride (2×300 mL) and brine (2×300 mL). After drying over sodium sulfate, the solvent was evaporated. The residue was purified using a silica gel column, eluting with hexane followed by 5% ethyl acetate in petroleum ether to yield 191 g (82%) of methyl 2-((trimethylsilyl)ethynyl)isonicotinate.

Workup

  1. customdried three necked flask which
  2. customwas twice purged with a stream of nitrogen
  3. customAt 20° C.
  4. stirringthe reaction mixture was stirred for further 2 hours at ambient temperature
  5. customThe precipitated residue was separated by filtration
  6. washtwice washed with diethyl ether (800 mL)
  7. washThe filtrate was washed with saturated ammonium chloride (2×300 mL) and brine (2×300 mL)
  8. dry with materialAfter drying over sodium sulfate
  9. customthe solvent was evaporated
  10. customThe residue was purified
  11. washeluting with hexane

Sources & evidence

ORD record
ord-94eee47020e8405abaa14335a77da0e7
Source dataset
uspto-grants-2012_10
Patent number
US08288405B2

Reaction notes

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