HomeMCPWorkbenchSkills
HomeWorkbenchNotificationsMe
llms.txt · MCP GuidePrivacy Policy · Terms of Service · Supportv1.8.0
  1. Home
  2. /Reaction

Diisopropylamine → 5-(2,4-Difluorophenyl)pyridine-3-carboxylic acid

HRID 1909144
Notes
Print preview

Reaction equation

HRID 1909144 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[F:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1B(O)O.[Na+].[Na+].[Na+].P(C1C=C(S([O-])(=O)=O)C=CC=1)(C1C=C(S([O-])(=O)=O)C=CC=1)C1C=C(S([O-])(=O)=O)C=CC=1.C(NC(C)C)(C)C>CN(C=O)C.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:11][C:12]1[CH:17]=[C:16]([F:18])[CH:15]=[CH:14][C:13]=1[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 887075-Bromonicotinic acidHCID 27343342,4-Difluorophenylboronic acidHCID 6099338Trisodium 3,3',3''-phosphinetriyltris(benzene-1-sulphonate)

Product 1

HCID 247297975-(2,4-Difluorophenyl)pyridine-3-carboxylic acidYield 111.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-bromonicotinic acid (0.5 g, 2.48 mmol) in DMF (7.4 mL) and water (2.5 mL) were added (2,4-difluorophenyl)boronic acid (0.43 g, 2.72 mmol), palladium acetate (27.8 mg, 0.12 mmol), 3,3′,3″-phosphinidynetris (benzensulfonic acid) trisodium salt (0.21 g, 0.37 mmol) and diisopropylamine (1.23 mL, 8.66 mmol). The mixture was heated to 80° C. After 1.5 h, the mixture was cooled to ambient temperature and filtered. The filtrate was purified by reverse chromatography (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid). The product was converted to hydrochloride salt by adding HCl (2.0 M in ether) and concentrated to give the hydrochloride salt of the title compound (0.65 g). MS 236.0 (M+1).

Workup

  1. temperaturethe mixture was cooled to ambient temperature
  2. filtrationfiltered
  3. customThe filtrate was purified by reverse chromatography (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid)
  4. additionby adding HCl (2.0 M in ether)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7f45f25ad0b64656b9e7951b3498a3f9
Source dataset
uspto-grants-2013_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08598209B2

Reaction notes

Loading…

On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes