Potassium Phosphate, Tribasic → 4-Fluoro-2-(2-nitro-5-(piperidin-1-yl)phenyl)pyridine

HRID 625387Notes

Reaction equation

HRID 625387 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)=[CH:6][C:5]=1B1OC(C)(C)C(C)(C)O1)([O-:3])=[O:2].Cl[C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][N:27]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>COCCOC.O.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>[F:32][C:30]1[CH:29]=[CH:28][N:27]=[C:26]([C:5]2[CH:6]=[C:7]([N:10]3[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]3)[CH:8]=[CH:9][C:4]=2[N+:1]([O-:3])=[O:2])[CH:31]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27827922-Chloro-4-fluoropyridineHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 66587487HCID 66587487, compound

Product 1

HCID 665867694-Fluoro-2-(2-nitro-5-(piperidin-1-yl)phenyl)pyridineYield 58.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Into a 500-mL 3-necked round bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 1-(4-nitro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine (15 g, 45.18 mmol, 1.00 equiv) in DME/H2O (100/5 mL), 2-chloro-4-fluoropyridine (7.80 g, 60.00 mmol, 1.20 equiv), K3PO4 (31 g, 146.23 mmol, 3.00 equiv), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (SPhos) (2.00 g, 4.88 mmol, 0.10 equiv), and Pd(PPh3)4 (2800 mg, 2.42 mmol, 0.05 equiv). The resulting solution was stirred for 1 overnight at 80° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 200 mL of H2O, extracted with 3×300 mL of dichloromethane, and the organic layers combined. The resulting mixture was washed with 1×20 mL of brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (10:1). The product was obtained as 8 g of a yellow solid.

Workup

  1. customInto a 500-mL 3-necked round bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. concentrationThe resulting mixture was concentrated under vacuum
  4. additionThe resulting solution was diluted with 200 mL of H2O
  5. extractionextracted with 3×300 mL of dichloromethane
  6. washThe resulting mixture was washed with 1×20 mL of brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated under vacuum
  9. washeluted with ethyl acetate/petroleum ether (10:1)

Sources & evidence

ORD record
ord-ea9d29b0e95e4d339266004b41c012a9
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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