3-Butyn-1-OL → 4-(4-Chloro-2-methoxy-phenyl)-but-3-yn-1-ol

HRID 2383996Notes

Reaction equation

HRID 2383996 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[O:9][CH3:10].[CH2:11]([OH:15])[CH2:12][C:13]#[CH:14]>N1CCCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C:14]#[C:13][CH2:12][CH2:11][OH:15])=[C:3]([O:9][CH3:10])[CH:4]=1

Participants

6

Reactant 2

HCID 135663-Butyn-1-OLHCID 179848451-Bromo-4-chloro-2-methoxybenzene

Product 1

HCID 591924974-(4-Chloro-2-methoxy-phenyl)-but-3-yn-1-olYield 77%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 31268PyrrolidineSolvent2×

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 2-bromo-5-chloroanisole (2 g, 9 mmol), Pd(PPh3)4 (520 mg, 0.45 mmol), and CuI (400 mg) in pyrrolidine (20 mL) was added a solution of 3-butyn-1-ol (1.26 g, 18 mmol) in pyrrolidine (30 mL). The reaction mixture was stirred at 80° C. for 6 h, and then concentrated in vacuo. The resulting residue was extracted with ethyl acetate and the organic phase was washed with 1N hydrochloric acid, followed by water, then brine, and dried over sodium sulfate. Upon removal of the solvent under reduced pressure, the crude product was subjected to column chromatography on silica gel (gradient elution with 0%-40% EtOAc/hexane) to give 4-(4-chloro-2-methoxy-phenyl)-but-3-yn-1-ol as a colorless oil (1.46 g, 76.7%). 1H NMR (300 MHz, CDCl3) δ ppm 7.29 (d, J=8.2 Hz, 1H), 6.88 (dd, J=8.2, 1.6 Hz, 1H), 6.85 (d, J=1.6 Hz, 1H), 3.87 (s, 3H), 3.82 (t, J=6.2 Hz, 2H), 2.73 (t, J=6.2 Hz, 2H), 1.92 (br. s, 1H).

Workup

  1. concentrationconcentrated in vacuo
  2. extractionThe resulting residue was extracted with ethyl acetate
  3. washthe organic phase was washed with 1N hydrochloric acid
  4. dry with materialbrine, and dried over sodium sulfate
  5. customUpon removal of the solvent under reduced pressure

Sources & evidence

ORD record
ord-8f7255a983da46bb96a281ca02e96eee
Source dataset
uspto-grants-2012_09
Patent number
US08263656B2

Reaction notes

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