Cesium carbonate → Ethyl 3-(4-chlorophenyl)propiolate

HRID 1799767Notes

Reaction equation

HRID 1799767 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:15]([O:17][C:18](=[O:21])[C:19]#[CH:20])[CH3:16]>[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>[CH2:15]([O:17][C:18](=[O:21])[C:19]#[C:20][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[CH3:16]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 12182Ethyl propiolate2×HCID 125101-Chloro-4-iodobenzene

Product 1

HCID 641307Ethyl 3-(4-chlorophenyl)propiolate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
35 °C

Procedure

Under argon atmosphere, a four neck flask was charged with 1-chloro-4-iodo-benzene (130.0 g, 0.55 mol), bis(triphenylphosphine) palladium(II) chloride (7.57 g, 10.8 mmol, 2 mol %), copper(I) iodide (4.19 g, 22.0 mmol, 4 mol %) and dry THF (1.4 l). At r.t., cesium carbonate (355.3 g, 1.09 mol, 2 eq.) was added over 5 min. Afterwards propynoic acid ethyl ester (111.3 ml, 1.09 mol, 2 eq.) was added, and the reaction mixture was stirred overnight at 35° C. An additional portion of propynoic acid ethyl ester (11.1 ml, 0.11 mol, 0.2 eq.) was added, and the reaction was stirred for another 3 h at 35° C. The reaction mixture was evaporated to dryness, and the residue was taken up in toluene (0.5 l) and heptane (1 l). The resulting suspension was stirred at 40° C. for 1 h and filtered over celite. The filtrate was concentrated, and the product purified by silica gel filtration (toluene/heptane 1:2) to yield 72.6 g (61%) of Va as a light yellow solid.

Workup

  1. stirringthe reaction was stirred for another 3 h at 35° C
  2. customThe reaction mixture was evaporated to dryness
  3. stirringThe resulting suspension was stirred at 40° C. for 1 h
  4. filtrationfiltered over celite
  5. concentrationThe filtrate was concentrated
  6. filtrationthe product purified by silica gel filtration (toluene/heptane 1:2)
  7. customto yield 72.6 g (61%) of Va as a light yellow solid

Sources & evidence

ORD record
ord-50d0992641e145c5b361a2357f4272ea
Source dataset
uspto-grants-2013_01
Patent number
US08344161B2

Reaction notes

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