Sodium Carbonate → Methyl 2-(2-nitro-5-(piperidin-1-yl)phenyl)isonicotinate

HRID 1407952Notes

Reaction equation

HRID 1407952 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.Br[C:27]1[CH:28]=[C:29]([CH:34]=[CH:35][N:36]=1)[C:30]([O:32][CH3:33])=[O:31].C(=O)([O-])[O-].[Na+].[Na+]>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>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15]2)=[CH:6][C:5]=1[C:27]1[CH:28]=[C:29]([CH:34]=[CH:35][N:36]=1)[C:30]([O:32][CH3:33])=[O:31])([O-:3])=[O:2]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 66587487HCID 66587487, compoundHCID 86705927Methyl 2-bromoisonicotinate hydrochloride

Product 1

HCID 66586744Methyl 2-(2-nitro-5-(piperidin-1-yl)phenyl)isonicotinate

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
95 °C

Procedure

Into a 250-mL 3-neck round bottom flask purged and maintained with an inert atmosphere of nitrogen, were placed a solution of 1-(4-nitro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidine (4 g, 12.05 mmol, 1.00 equiv) in ethylene glycol dimethyl ether (60 mL), methyl 2-bromoisonicotinate hydrochloride (2.6 g, 12.09 mmol, 1.02 equiv), a solution of sodium carbonate (6.4 g, 60.38 mmol, 5.01 equiv) in water (30 mL), and Pd(PPh3)4 (1.4 g, 1.21 mmol, 0.10 equiv). The resulting solution was stirred for 3 h at 95° C. The resulting solution was diluted with 100 mL of water. The resulting solution was extracted with 3×100 mL of ethyl acetate and the organic layers combined. The resulting mixture was washed with 3×100 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with petroleum ether/ethyl acetate (10:1). This resulted in 1.8 g (44%) of methyl 2-(2-nitro-5-(piperidin-1-yl)phenyl)isonicotinate as a red semi-solid.

Workup

  1. customInto a 250-mL 3-neck round bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. extractionThe resulting solution was extracted with 3×100 mL of ethyl acetate
  4. washThe resulting mixture was washed with 3×100 mL of brine
  5. dry with materialThe mixture was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum
  7. washeluted with petroleum ether/ethyl acetate (10:1)
  8. customThis resulted in 1.8 g (44%) of methyl 2-(2-nitro-5-(piperidin-1-yl)phenyl)isonicotinate as a red semi-solid

Sources & evidence

ORD record
ord-e78334a8116946ccb9be32f31680ce1b
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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