Triethylamine → 3-Bromo-5-(3-methoxy-prop-1-ynyl)-4-methyl-benzoic acid
Reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9](I)[C:10]=1[CH3:11])[C:5]([OH:7])=[O:6].C(N(CC)CC)C.[CH3:20][O:21][CH2:22][C:23]#[CH:24]>C1COCC1.CC(OC)(C)C.O.[Cu](I)I.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>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:24]#[C:23][CH2:22][O:21][CH3:20])[C:10]=1[CH3:11])[C:5]([OH:7])=[O:6]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 5
Conditions
- Temperature
- 65 °C
Procedure
To a stirred solution of 3-bromo-5-iodo-4-methyl-benzoic acid in THF (0.98 M) was added triethylamine (7.5 equiv.) and copper iodide (0.01 equiv.) followed by PdCl2(PPh3)2 (0.005 equiv). Propargyl methyl ether (1.5 equiv.) was then added and the mixture heated to ˜65° C. for ˜24 h. The mixture was cooled to 20° C. and then diluted with MTBE and water. The layers were cut and the organic washed with further water. The combined aqueous layers were mixed with further MTBE and 5 N HCl. The organic layer was washed with 1M HCl, twice with 3% w/v sodium bisulfite and finally with water. The resultant solution was concentrated to ˜0.38 M and used in the next step as a solution in THF. 1H NMR (400 MHz, Acetone-d6): δ 8.13 (s, 1 H); 8.00 (s, 1 H); 4.40 (s, 2 H); 3.41 (s, 3 H); 2.59 (s, 3 H). FIRMS (ES, M−H) Calcd 280.9813. Found 280.9820.
Workup
- temperatureThe mixture was cooled to 20° C.
- washthe organic washed with further water
- additionThe combined aqueous layers were mixed with further MTBE and 5 N HCl
- washThe organic layer was washed with 1M HCl, twice with 3% w/v sodium bisulfite and finally with water
- concentrationThe resultant solution was concentrated to ˜0.38 M
Sources & evidence
- ORD record
- ord-f987f167f0134e8a9b99eedd746e156b
- Source dataset
- uspto-grants-2014_11
- Patent number
- US08889714B2
Reaction notes
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