Cesium carbonate → Ethyl 5-(3-chloro-5-fluorophenyl)-4-(3-cyano-4-fluorophenyl)thiophene-2-carboxylate

HRID 1036991Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[S:5][C:6]=1[C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[C:9]([Cl:14])[CH:8]=1.[C:20]([C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][C:27]=1[F:28])#[N:21].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:14][C:9]1[CH:8]=[C:7]([C:6]2[S:5][C:4]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:3][C:2]=2[C:24]2[CH:25]=[CH:26][C:27]([F:28])=[C:22]([C:20]#[N:21])[CH:23]=2)[CH:12]=[C:11]([F:13])[CH:10]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Under argon, 220 mg (0.61 mmol) of the compound from Example 9A are provided in 6.2 ml of 1,2-dimethoxyethane, and 100 mg (0.61 mmol) of 3-cyano-4-fluorophenylboronic acid, 593 mg (1.82 mmol) of cesium carbonate, 20.0 mg (0.04 mmol) of dicyclohexyl[2′,4′,6′-tri(propan-2-yl)biphenyl-2-yl]phosphane and 4.0 mg (0.02 mmol) of palladium(II) acetate are added. The mixture is stirred at 50° C. overnight. The same amount of catalyst and ligand is added once more, and the mixture is stirred at 50° C. overnight. The reaction mixture is purified by preparative HPLC (RP18 column; eluent: acetonitrile/water gradient with addition of 0.1% formic acid). 86.0 mg (35% of theory) of the title compound are obtained.

Workup

additionThe same amount of catalyst and ligand is added once more
stirringthe mixture is stirred at 50° C. overnight
customThe reaction mixture is purified by preparative HPLC (RP18 column; eluent: acetonitrile/water gradient with addition of 0.1% formic acid)

Sources & evidence

ORD record: ord-303e770d4c2442399386484911a0bc10
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546438B2

Reaction notes

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