Hydrochloric Acid → 5-(3-Chloro-4-fluorophenyl)-6-(2,2,2-trifluoroethoxy)nicotinic acid

HRID 1025983Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:14]([OH:16])=[O:15])[CH:5]=[N:6][C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].[Cl:17][C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[CH:22][C:23]=1[F:24].C([O-])([O-])=O.[Na+].[Na+].Cl>C1(C)C=CC=CC=1.CN(C=O)C>[Cl:17][C:18]1[CH:19]=[C:20]([C:2]2[C:7]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])=[N:6][CH:5]=[C:4]([CH:3]=2)[C:14]([OH:16])=[O:15])[CH:21]=[CH:22][C:23]=1[F:24]

Participants

Conditions

Temperature: 90 °C

Procedure

5-Bromo-6-(2,2,2-trifluoroethoxy)-3-pyridinecarboxylic acid (CAN 1211586-75-2; 1.5 g; 5.0 mmol) was dissolved in toluene (35 mL) an DMF (2 mL). To this solution was added 1,1′-bis(diphenylphosphino)-ferrocene-palladium(II)dichloride dichloromethane complex (204 mg, 250 μmol), followed by 3-chloro-4-fluorophenylboronic acid (CAN 144432-85-9; 959 mg, 5.5 mmol) and 2M—Na2CO3 (20.0 ml, 40.0 mmol). The reaction mixture was heated to 90° C. and stirred for 4 h, cooled and poured into 100 mL ice water, acidified with 45 mL 2N—HCl and extracted ethyl acetate. The organic layers were combined, dried with Na2SO4 and concentrated in vacuo. The crude material was crystallized from heptane:ethyl acetate (5:1) to yield 1.1 g (63%) of the title compound as light grey solid; LC-MS (UV peak area/ESI): 97%, 348.0066 (M−H)−.

Workup

additionTo this solution was added 1,1′-bis(diphenylphosphino)-ferrocene-palladium(II)dichloride dichloromethane complex (204 mg, 250 μmol)
temperaturecooled
extractionextracted ethyl acetate
dry with materialdried with Na2SO4
concentrationconcentrated in vacuo
customThe crude material was crystallized from heptane:ethyl acetate (5:1)

Sources & evidence

ORD record: ord-1594cc1689c24116879ad165bd283b5f
Source dataset: uspto-grants-2014_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08729105B2

Reaction notes

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