alpha-Ethynylbenzenemethanol → HCID 10238395, compound

HRID 1814894Notes

Reaction equation

HRID 1814894 reaction equation
Br[C:2]1[O:23][C:5]2[N:6]([CH3:22])[CH:7]=[C:8]([C:11]([NH:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=3)=[O:12])[C:9](=[O:10])[C:4]=2[CH:3]=1.[C:24]1([CH:30]([OH:33])[C:31]#[CH:32])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C(N(CC)CC)C.CN(C=O)C.[Cu]I.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>[Cl:21][C:18]1[CH:19]=[CH:20][C:15]([CH2:14][NH:13][C:11]([C:8]2[C:9](=[O:10])[C:4]3[CH:3]=[C:2]([C:32]#[C:31][CH:30]([OH:33])[C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[O:23][C:5]=3[N:6]([CH3:22])[CH:7]=2)=[O:12])=[CH:16][CH:17]=1

Participants

7

Reactant 2

HCID 20155alpha-EthynylbenzenemethanolHCID 10237594HCID 10237594, compound

Product 1

HCID 10238395HCID 10238395, compound

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

2-Bromo-N-(4-chlorobenzyl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]-pyridine-5-carboxamide (Example 79, 0.593 g) was suspended in a mixture of triethylamine (15 mL) and DMF (3 mL). CuI (0.029 g), Pd(PPh3)2Cl2 (0.105 g), and then 1-phenyl-2-propyn-1-ol (0.36 mL) were added. The reaction mixture was stirred at room temperature for 30 min and then was partitioned between CH2Cl2 (50 mL) and water (50 mL). The aqueous layer was separated and then extracted with CH2Cl2 (3×50 mL). The combined organic layers were washed with a sat. aq. ammonium chloride solution (100 mL), dried (MgSO4), filtered, and concentrated in vacuo. The resulting solid was purified by column chromatography (CH2Cl2/methanol; 99/1, 98/2) followed by recrystallization from methanol to yield 0.260 g of the title compound as a yellow solid. Physical characteristics. M.p. 209-211° C. (dec); 1H NMR (400 MHz, DMSO-d6) δ 10.48, 8.60, 7.53-7.51, 7.43-7.32, 6.43, 5.73, 4.55, 3.91; MS (ESI+) m/z 447 (M+H)+.

Workup

  1. customwas partitioned between CH2Cl2 (50 mL) and water (50 mL)
  2. customThe aqueous layer was separated
  3. extractionextracted with CH2Cl2 (3×50 mL)
  4. washThe combined organic layers were washed with a sat. aq. ammonium chloride solution (100 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting solid was purified by column chromatography (CH2Cl2/methanol; 99/1, 98/2)
  9. customfollowed by recrystallization from methanol

Sources & evidence

ORD record
ord-453726e2aab040599b52ac979ed83c18
Source dataset
uspto-grants-2005_04
Patent number
US06878705B2

Reaction notes

Loading…