(1,1-Dimethylprop-2-ynyloxy)acetic acid methyl ester → [3-(4'-Chloro-4-methylbiphenyl-3-yl)-1,1-dimethylprop-2-ynyloxy]acetic acid methyl ester

HRID 1470855Notes

Reaction equation

HRID 1470855 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[CH3:8].[CH3:16][O:17][C:18](=[O:26])[CH2:19][O:20][C:21]([CH3:25])([CH3:24])[C:22]#[CH:23]>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>[CH3:16][O:17][C:18](=[O:26])[CH2:19][O:20][C:21]([CH3:24])([CH3:25])[C:22]#[C:23][C:2]1[CH:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[CH3:8]

Participants

6

Reactant 2

HCID 13005744(1,1-Dimethylprop-2-ynyloxy)acetic acid methyl esterHCID 594459301-Bromo-5-(4-chlorophenyl)-2-methylbenzene

Product 1

HCID 58312427[3-(4'-Chloro-4-methylbiphenyl-3-yl)-1,1-dimethylprop-2-ynyloxy]acetic acid methyl esterYield 42%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

To a solution of 3-bromo-4′-chloro-4-methylbiphenyl (12.6 g, 44.7 mmol) and (1,1-dimethylprop-2-ynyloxy)acetic acid methyl ester (prepared according to WO2001/066544) (8.4 g, 53.8 mmol) in triethylamine (70 ml) is added bis(triphenylphosphine)palladium(II) dichloride (0.63 g, 0.9 mmol) and copper(I) iodide (0.34 g, 1.8 mmol). The reaction mixture is degassed and flushed with nitrogen (×3), then stirred under nitrogen at 80° C. for one hour. The cooled mixture is filtered through diatomaceous earth to remove the catalyst, and the filtrate evaporated in vacuo. The residue is resubjected to the same reaction conditions (8.4 g 1,1-dimethylprop-2-ynyloxy)acetic acid methyl ester, 0.63 g bis(triphenylphosphine)-palladium(II) dichloride, 0.34 g copper(I) iodide in 70 ml triethylamine under nitrogen) and stirred at 80° C. for one hour. The cooled mixture is filtered through diatomaceous earth, then concentrated in vacuo and purified by flash chromatography (hexane/ethyl acetate 3:1) to afford [3-(4′-chloro-4-methylbiphenyl-3-yl)-1,1-dimethylprop-2-ynyloxy]acetic acid methyl ester (6.70 g,) as an oil.

Workup

  1. customThe reaction mixture is degassed
  2. customflushed with nitrogen (×3)
  3. filtrationThe cooled mixture is filtered through diatomaceous earth
  4. customto remove the catalyst
  5. customthe filtrate evaporated in vacuo
  6. customThe residue is resubjected to the same reaction conditions (8.4 g 1,1-dimethylprop-2-ynyloxy)acetic acid methyl ester, 0.63 g bis(triphenylphosphine)-palladium(II) dichloride, 0.34 g copper(I) iodide in 70 ml triethylamine under nitrogen) and
  7. stirringstirred at 80° C. for one hour
  8. filtrationThe cooled mixture is filtered through diatomaceous earth
  9. concentrationconcentrated in vacuo
  10. custompurified by flash chromatography (hexane/ethyl acetate 3:1)

Sources & evidence

ORD record
ord-40076bc45b6e4d43a04664adf30b8846
Source dataset
uspto-grants-2015_04
Patent number
US09006429B2

Reaction notes

Loading…