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

HRID 1037003Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[S:5][C:6]=1Br.[F:13][C:14]1[CH:15]=[C:16]([C:29]#[N:30])[CH:17]=[C:18](B2OC(C)(C)C(C)(C)O2)[CH:19]=1.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.O>[Br:1][C:2]1[CH:3]=[C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[S:5][C:6]=1[C:18]1[CH:19]=[C:14]([F:13])[CH:15]=[C:16]([C:29]#[N:30])[CH:17]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Under argon, 1.50 g (4.78 mmol) of the compound from Example 8A are provided in 75 ml of 1,2-dimethoxyethane, and 1.30 g (5.26 mmol) of the compound from Example 5A, 4.67 g (14.3 mmol) of cesium carbonate, 159 mg (0.33 mmol) of dicyclohexyl[2′,4′,6′-tri(propan-2-yl)biphenyl-2-yl]phosphane and 32.0 mg (0.14 mmol) of palladium(II) acetate are added. The mixture is stirred at 50° C. overnight. Water is subsequently added, the mixture is extracted with ethyl acetate and the extract is dried over sodium sulfate, filtered and concentrated. The crude product is purified by preparative HPLC (RP18 column; eluent: acetonitrile/water gradient with addition of 0.1% formic acid). 1.05 g of ethyl 4-bromo-5-(3-cyano-5-fluorophenyl)thiophene-2-carboxylate are obtained.

Workup

extractionthe mixture is extracted with ethyl acetate
dry with materialthe extract is dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe crude product is purified by preparative HPLC (RP18 column; eluent: acetonitrile/water gradient with addition of 0.1% formic acid)

Sources & evidence

ORD record: ord-36c8904c00114acba6b34c82c31a60ec
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546438B2

Reaction notes

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