Propargyl alcohol → Methyl 3-(3-hydroxyprop-1-yn-1-yl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxylate

HRID 1473246Notes

Reaction equation

HRID 1473246 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:9][C:8]2[CH2:10][CH2:11][CH2:12][CH2:13][C:7]=2[C:6]=1I)=[O:4].[CH2:15]([OH:18])[C:16]#[CH:17].C(N(CC)CC)C>C(#N)C.[Cu]I>[CH3:1][O:2][C:3]([C:5]1[S:9][C:8]2[CH2:10][CH2:11][CH2:12][CH2:13][C:7]=2[C:6]=1[C:17]#[C:16][CH2:15][OH:18])=[O:4]

Participants

6

Reactant 3

HCID 7859Propargyl alcoholHCID 8471TriethylamineHCID 89463240Methyl 3-iodo-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxylate

Product 1

HCID 89463106Methyl 3-(3-hydroxyprop-1-yn-1-yl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxylateYield 73%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 3-Iodo-4,5,6,7-tetrahydro-benzo[b]thiophene-2-carboxylic acid methyl ester (15 g, 46.6 mmol) and prop-2-yn-1-ol (5.22 g, 93 mmol) in Acetonitrile (100 mL) was added Pd(PPh3)2Cl (3.27 g, 4.66 mmol), copper(I) iodide (0.89 g, 4.66 mmol) and triethylamine (14 g, 140 mmol). The mixture was heated at 85° C. reflux under N2 for 3 hrs. The reaction was cooled to room temperature, and concentrated to dryness, which was diluted with H2O (50 mL), extracted with ethyl acetate (200 mL×3), The organic phase was washed with saturated aqueous NaHCO3 150 mL, dried over Na2SO4, After concentration, the crude product was purified by silica gel chromatography eluted with PE:EtOAc=10:1-4:1 to give afford title product (8.5 g, 73% yield) as yellow oil. LCMS (m/z) ES+=233 (M+1).

Workup

  1. temperaturereflux under N2 for 3 hrs
  2. temperatureThe reaction was cooled to room temperature
  3. concentrationconcentrated to dryness, which
  4. additionwas diluted with H2O (50 mL)
  5. extractionextracted with ethyl acetate (200 mL×3)
  6. washThe organic phase was washed with saturated aqueous NaHCO3 150 mL
  7. dry with materialdried over Na2SO4
  8. concentrationAfter concentration
  9. customthe crude product was purified by silica gel chromatography
  10. washeluted with PE
  11. customEtOAc=10:1-4:1 to give

Sources & evidence

ORD record
ord-6b6ccffdfae9496790fbc2df49ba82ab
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

Loading…