Phenylacetylene → HCID 118414926, compound

HRID 1054313Notes

Reaction equation

HRID 1054313 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:5]2[C:10]([CH3:11])=[N:9][N:8]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[CH:15][CH:14]=3)[C:6]=2[N:7]=1.[C:31]1([C:37]#[CH:38])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>CCN(CC)CC.C1COCC1.CCOC(C)=O.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>[CH3:11][C:10]1[C:5]2[C:4]([C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:3][C:2]([C:38]#[C:37][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[N:7][C:6]=2[N:8]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:15][CH:14]=2)[N:9]=1

Participants

8

Reactant 2

HCID 10821PhenylacetyleneHCID 118414928HCID 118414928, compound

Product 1

HCID 118414926HCID 118414926, compoundYield 31%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

(see, e.g., Dai, W., et al., Org Lett 2006, 8, 4665-7). A mixture of 50 (95 mg, 0.22 mmol), Pd(PPh3)2Cl2 (16 mg, 0.02 mmol), and CuI (8.6 mg, 0.04 mmol) in Et3N (0.5 mL) and dry THF (1 mL) was added dropwise to a solution of phenylacetylene (40 μL, 0.36 mmol) in Et3N (0.5 mL) under nitrogen at room temperature. Reaction mixture was heated to 60° C. and stirred overnight then diluted with EtOAc (10 mL) and washed with saturated aqueous NH4Cl (15 mL×2) and brine (15 mL). The organic layer was dried (Na2SO4), filtered, concentrated under reduced pressure. The crude was purified by flash column chromatography on silica gel to give the title compound (33 mg, 31%) as an orange oil. 1H NMR (500 MHz, CDCl3) δ 7.81 (s, 1H), 7.68-7.63 (m, 2H), 7.42-7.37 (m, 3H), 7.35-7.29 (m, 4H), 7.08 (t, J=7.6 Hz, 1H), 6.97 (d, J=8.4 Hz, 2H), 6.93 (d, J=8.4 Hz, 2H), 5.68 (s, 2H), 4.50 (q, J=7.1 Hz, 2H), 2.72 (s, 3H), 1.47 (t, J=7.1 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 165.08, 157.02, 156.83, 152.00, 141.84, 141.44, 133.56, 132.20, 131.77, 129.69, 129.47, 129.36, 128.45, 123.28, 121.86, 121.06, 118.94, 118.81, 110.56, 90.88, 88.87, 62.09, 49.81, 16.24, 14.26.

Workup

  1. customReaction mixture
  2. washwashed with saturated aqueous NH4Cl (15 mL×2) and brine (15 mL)
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude was purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-1152f55ccfd24639975b20a56edeb1dd
Source dataset
uspto-grants-2016_07
Patent number
US09394303B2

Reaction notes

Loading…