Sodium Carbonate → 5-(4-Fluorophenyl)pyridine-3-carboxylic acid morpholinamide

HRID 490967Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.[N:11]1([C:17]([NH2:19])=[O:18])[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1.Br[C:21]1[CH:22]=[N:23][CH:24]=[C:25]([CH:29]=1)[C:26]([OH:28])=[O:27].C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.O>[N:11]1([C:17]([NH2:19])=[O:18])[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1.[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:21]2[CH:29]=[C:25]([C:26]([OH:28])=[O:27])[CH:24]=[N:23][CH:22]=2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 65 °C

Procedure

1.2 g of Pd[P(Ph)3]4 and 7.6 g of p-fluorobenzeneboronic acid are added to a solution of 14.3 g of 5-bromonicotinic acid morpholinamide in 100 g of THF. A solution of 8.0 g of Na2CO3 in 25 g of water is subsequently added dropwise with stirring at 65° C. After 16 hours, the reaction mixture is cooled and evaporated in a rotary evaporator. The residue is taken up in dichloromethane, activated carbon is added, and the mixture is filtered. Repeated extraction of the filtrate with water and evaporation in a rotary evaporator gives a residue of 15.7 g, which, according to HPLC, comprises 89% of 5-(4-fluorophenyl)pyridine-3-carboxylic acid morpholinamide (net yield 93% of theory). Recrystallisation from ethyl acetate gives 8.0 g of 5-(4-fluorophenyl)pyridine-3-carboxylic acid morpholinamide having an HPLC purity of 99.6% (53.3% of theory).

Workup

temperaturethe reaction mixture is cooled
customevaporated in a rotary evaporator
additionactivated carbon is added
filtrationthe mixture is filtered
extractionextraction of the filtrate
customwith water and evaporation
customin a rotary evaporator
customgives a residue of 15.7 g, which

Sources & evidence

ORD record: ord-f83d971deb4045518f110f7e9e19ada6
Source dataset: uspto-grants-2009_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07528256B2

Reaction notes

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