2-Methyl-3-butyn-2-ol → 4-(3-(3-Hydroxypropyl)phenyl)-2-methylbut-3-yn-2-ol

HRID 2172747Notes

Reaction equation

HRID 2172747 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][CH2:10][OH:11])[CH:5]=[CH:6][CH:7]=1.[CH3:12][C:13]([OH:17])([C:15]#[CH:16])[CH3:14]>C(N(CC)CC)C.[Cu]I>[OH:11][CH2:10][CH2:9][CH2:8][C:4]1[CH:3]=[C:2]([C:16]#[C:15][C:13]([CH3:14])([OH:17])[CH3:12])[CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 2

HCID 82582-Methyl-3-butyn-2-olHCID 187859283-(3-Bromophenyl)propan-1-ol

Product 1

HCID 576085154-(3-(3-Hydroxypropyl)phenyl)-2-methylbut-3-yn-2-ol

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
70 °C

Procedure

To a degassed solution of 3-(3-bromophenyl)propan-1-ol (47) (0.95 g, 4.5 mmol) and 2-methyl-3-butyn-2-ol (48) (1.6 mL, 16 mmol) in triethylamine (25 mL) was added PdCl2(PPh3)3 (0.095 g, 0.14 mmol) and CuI (0.027 g, 0.14 mmol). The resulting mixture was degassed and stirred under argon at 70° C. for 15 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure and diluted with EtOAc (50 mL). Trace solids were removed by filtration then the filtrate was washed with water and brine, dried over Na2SO4, and concentrated under reduced pressure. Purification by flash chromatography (10 to 100% EtOAc-hexanes gradient) gave 4-(3-(3-hydroxypropyl)phenyl)-2-methylbut-3-yn-2-ol (49) as a light brown oil: Yield (0.78 g, 80%): 1H NMR (400 MHz, DMSO-d6) δ 7.18-7.29 (m, 4H), 5.46 (s, 1H), 4.48 (t, J=4.0 Hz, 1H), 3.38 (q, J=4.0 Hz, 2H), 2.59 (t, J=6.0 Hz, 2H), 2.46 (m, 2H), 1.46 (s, 6H).

Workup

  1. customThe resulting mixture was degassed
  2. temperatureAfter cooling to room temperature
  3. concentrationthe reaction mixture was concentrated under reduced pressure
  4. additiondiluted with EtOAc (50 mL)
  5. customTrace solids were removed by filtration
  6. washthe filtrate was washed with water and brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customPurification by flash chromatography (10 to 100% EtOAc-hexanes gradient)

Sources & evidence

ORD record
ord-2b07e775dbf44e7590deb9ea570db002
Source dataset
uspto-grants-2015_06
Patent number
US09056849B2

Reaction notes

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