Cesium carbonate → (4-Chloro-3-fluoro-phenyl)-propynoic acid ethyl ester
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][C:3]=1[F:9].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:16]([O:18][C:19](=[O:22])[C:20]#[CH:21])[CH3:17]>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I.C1COCC1>[CH2:16]([O:18][C:19](=[O:22])[C:20]#[C:21][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([F:9])[CH:4]=1)[CH3:17]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 35 °C
Procedure
Under argon atmosphere, a four neck flask was charged with 1-chloro-2-fluoro-4-iodo-benzene (50.5 g, 0.20 mol), bis(triphenylphosphine) palladium(II) chloride (2.76 g, 3.94 mmol, 2 mol %), copper(I) iodide (1.50 g, 7.80 mol, 4 mol %) and dry THF (600 ml). At r.t., cesium carbonate (128.3 g, 0.39 mol, 2 eq.) was added over 5 min. Finally, propynoic acid ethyl ester (38.6 g, 0.39 mol, 2 eq.) was added, and the reaction was stirred for 48 h at 35° C. The reaction mixture was evaporated to dryness, and the residue was taken up in toluene (50 ml) and heptane (100 ml). The resulting suspension was stirred at 40° C. for 1 h and filtered afterward over celite. The filtrate was concentrated, and the product was purified by silica gel filtration (toluene/heptane 1:2) to yield 38.8 g (87%) of the Vd as a light yellow solid.
Workup
- customThe reaction mixture was evaporated to dryness
- stirringThe resulting suspension was stirred at 40° C. for 1 h
- filtrationfiltered afterward over celite
- concentrationThe filtrate was concentrated
- filtrationthe product was purified by silica gel filtration (toluene/heptane 1:2)
- customto yield 38.8 g (87%) of the Vd as a light yellow solid
Sources & evidence
- ORD record
- ord-ad38d81ad3e04c7fbb36c53fb5e9bd87
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08344161B2
Reaction notes
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