Triethylamine → [4-(4-Cyanophenyl)but-3-ynyl]carbamic acid tert-butyl ester

HRID 81339

Reaction equation

HRID 81339 reaction equation
[C:1]([O:5][C:6](=[O:12])[NH:7][CH2:8][CH2:9][C:10]#[CH:11])([CH3:4])([CH3:3])[CH3:2].I[C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=1.C(N(CC)CC)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.C1COCC1>[C:1]([O:5][C:6](=[O:12])[NH:7][CH2:8][CH2:9][C:10]#[C:11][C:14]1[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 764674-IodobenzonitrileHCID 10725815tert-Butyl 3-butyn-1-ylcarbamate

Product 1

HCID 67364707[4-(4-Cyanophenyl)but-3-ynyl]carbamic acid tert-butyl esterYield 99%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

But-3-ynylcarbamic acid tert-butyl ester (3.66 g, 22 mmol) was added dropwise to an ice cooled, stirring, argon purged mixture of 4-iodobenzonitrile (4.5 g, 19.6 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.69 g, 0.98 mmol), copper (1) iodide (0.19 g, 0.98 mmol), triethylamine (11 mL, 78.4 mmol), and THF (24 mL). After stirring for 10 min, the ice bath was removed, and the reaction was allowed to stir for an additional 2 h. The reaction mixture was passed through a pad of silica gel with methylene chloride/ethyl acetate (5:1) as eluant. After evaporating the solvent, the crude product was chromatographed with methylene chloride/ethyl acetate (20:1) as eluant. Evaporation of the solvent, followed by placement under vacuum for 1 h, afforded the pure product 56 (5.2 g, 99%) as an oil. 1H NMR (300 MHz, CDCl3) δ 1.46 (s, 9H), 2.64 (t, 2H), 3.37 (m, 2H), 4.85 (br s, 1H), 7.47 (d, 2H), 7.58 (d, 2H).

Workup

  1. temperaturecooled
  2. customargon purged
  3. stirringAfter stirring for 10 min
  4. customthe ice bath was removed
  5. stirringto stir for an additional 2 h
  6. customAfter evaporating the solvent
  7. customthe crude product was chromatographed with methylene chloride/ethyl acetate (20:1) as eluant
  8. customEvaporation of the solvent

Sources & evidence

ORD record
ord-5e656e4dfbef4f54b82be3b57cef2ec3
Source dataset
uspto-grants-2014_09
Patent number
US08846688B2

Linked notes

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