Sodium Bicarbonate → 4-(3-Chloro-4-fluorophenyl)-5-(3-chloro-5-fluorophenyl)-1,3-thiazole-2-carboxylic acid

HRID 2038366Notes

Reaction equation

Br[C:2]1[S:6][C:5]([C:7]([O:9]CC)=[O:8])=[N:4][C:3]=1[C:12]1[CH:17]=[CH:16][C:15]([F:18])=[C:14]([Cl:19])[CH:13]=1.[Cl:20][C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[C:25]([F:27])[CH:26]=1.C(=O)(O)[O-].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:19][C:14]1[CH:13]=[C:12]([C:3]2[N:4]=[C:5]([C:7]([OH:9])=[O:8])[S:6][C:2]=2[C:23]2[CH:24]=[C:25]([F:27])[CH:26]=[C:21]([Cl:20])[CH:22]=2)[CH:17]=[CH:16][C:15]=1[F:18]

Participants

Conditions

Temperature: 80 °C

Procedure

Under argon, 100 mg (0.27 mmol) of the compound from Example 4A are provided in 4 ml of 1,2-dimethoxyethane, and 71.7 mg (0.41 mmol) of 3-chloro-5-fluorophenylboronic acid, 1.5 ml (1.37 mmol) of an aqueous sodium bicarbonate solution (10%) and 9.5 mg (8 μmol) of tetrakis(triphenylphosphine)palladium(0) are added. The mixture is stirred at 80° C. overnight. The mixture is concentrated and the residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient), and 93.0 mg (88% of theory) of the title compound are obtained.

Workup

concentrationThe mixture is concentrated
customthe residue is purified by preparative HPLC (RP18 column; mobile phase: acetonitrile/water gradient), and 93.0 mg (88% of theory) of the title compound
customare obtained

Sources & evidence

ORD record: ord-cbb8f05aa5554a61b774aa9732f5cfee
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08575357B2

Reaction notes

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