Triethylamine → {4-Chloro-2-[(2-methoxyphenyl)ethynyl]phenoxy}acetic acid

HRID 2390324Notes

Reaction equation

Br[C:2]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:3]=1[O:4][CH2:5][C:6]([OH:8])=[O:7].[C:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[O:22][CH3:23])#[CH:15].C(N(CC)CC)C>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)I.C(#N)C>[Cl:13][C:11]1[CH:10]=[CH:9][C:3]([O:4][CH2:5][C:6]([OH:8])=[O:7])=[C:2]([C:15]#[C:14][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[O:22][CH3:23])[CH:12]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A solution of (2-bromo-4-chlorophenoxy)acetic acid (200 mg; 0.75 mmol, Intermediate 4) and 2-ethynylanisole (Aldrich, 107 μL; 0.83 mmol) in anhydrous, degassed ACN (2 mL) was treated with dichlorobis(triphenylphosphine)palladium(II) (38 mg; 0.05 mmol) followed after 5 minutes by copper iodide (10 mg; 0.05 mmol) and triethylamine (0.45 mL; 3.3 mmol). The reaction mixture was heated at 50° C. under stirring for 16 hours. The solvents were removed under vacuum, the residue was then taken up in EtOAc and washed with HCl (1N aqueous solution), the organic phase was washed with water (750 mL) then with brine (750 mL), dried over MgSO4, filtered and concentrated under vacuum to give a brown oily residue which was purified by preparative HPLC to afford the title compound as a brown oil.

Workup

customThe solvents were removed under vacuum
washwashed with HCl (1N aqueous solution)
washthe organic phase was washed with water (750 mL)
dry with materialwith brine (750 mL), dried over MgSO4
filtrationfiltered
concentrationconcentrated under vacuum
customto give a brown oily residue which
customwas purified by preparative HPLC

Sources & evidence

ORD record: ord-3bd75bb6f1d7480c87ebb2d18adc6b9c
Source dataset: uspto-grants-2012_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08273769B2

Reaction notes

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