Diisopropylamine → tert-butyl 4-((trimethylsilyl)ethynyl)-1H-pyrazole-1-carboxylate

HRID 2205851Notes

Reaction equation

HRID 2205851 reaction equation
I[C:2]1[CH:3]=[N:4][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH:6]=1.[CH3:14][Si:15]([C:18]#[CH:19])([CH3:17])[CH3:16].C(NC(C)C)(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.[Cu]I.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:14][Si:15]([C:18]#[C:19][C:2]1[CH:3]=[N:4][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH:6]=1)([CH3:17])[CH3:16]

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 11776TriphenylphosphineHCID 66111TrimethylsilylacetyleneHCID 177502241-Boc-4-iodopyrazole

Product 1

HCID 68478797tert-butyl 4-((trimethylsilyl)ethynyl)-1H-pyrazole-1-carboxylateYield 92.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

tert-Butyl 4-iodo-1H-pyrazole-1-carboxylate (2) (4.67 g 15.9 mmole) and trimethylsilyl acetylene (2.18 g, 22.2 mmole) were dissolved in DMF (22 mL) and placed under argon. Diisopropylamine (2.9 mL, 2.08 g, 20.7 mmole), copper(I) iodide (197 mg, 1.03 mmole), triphenylphosphine (832 mg, 3.18 mmole) and palladium acetate (239 mg, 1.06 mmole) were added and the flask was flushed again with argon. The reaction was heated at 60° C. for 1.25 hours. The reaction was cooled and added to water (220 mL). The product was extracted with ether (3×60 mL). The combined extracts were washed with water (3×50 mL) and with brine, then dried and evaporated. The crude product was flash chromatographed (silica, eluting with 10% ethyl acetate in cyclohexane) to give the title compound (3.88 g, 92%). 1H-NMR (CDCl3, 500 MHz): δ 0.25 (s, 6H), 1.67 (s, 9H), 7.77 (d, J=0.63 Hz, 1H), 8.20 (d, J=0.63 Hz, 1H).

Workup

  1. customthe flask was flushed again with argon
  2. temperatureThe reaction was cooled
  3. additionadded to water (220 mL)
  4. extractionThe product was extracted with ether (3×60 mL)
  5. washThe combined extracts were washed with water (3×50 mL) and with brine
  6. customdried
  7. customevaporated
  8. customchromatographed
  9. wash(silica, eluting with 10% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-c4abc159840d4bf8b76e539b8c9be6eb
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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