Potassium Carbonate → 4-(4-Amino-3-fluorophenoxy)picolinonitrile

HRID 1711622Notes

Reaction equation

HRID 1711622 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].CC(C)([O-])C.[Na+].Cl[C:17]1[CH:22]=[CH:21][N:20]=[C:19]([C:23]#[N:24])[CH:18]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:17]2[CH:22]=[CH:21][N:20]=[C:19]([C:23]#[N:24])[CH:18]=2)=[CH:4][C:3]=1[F:9]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 6933424-Chloro-2-pyridinecarbonitrileHCID 27359194-Amino-3-fluorophenolHCID 23676156Sodium t-butoxide

Product 1

HCID 551566584-(4-Amino-3-fluorophenoxy)picolinonitrileYield 31%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A teflon capped vial was charged with 4-amino-3-fluorophenol (0.291 g, 2.29 mmol) and anhydrous DMF (2.3 mL). The resultant solution was de-gassed in vacuo and backfilled with argon (3×). The vial was treated with sodium tert-butoxide (0.27 g, 2.41 mmol) under argon and quickly capped. The reaction mixture was stirred at RT for 1 h. After addition of 4-chloropicolinonitrile (0.317 g, 2.29 mmol) and K2CO3 (0.174 g, 1.26 mmol), the vial was de-gassed again and heated in a 90° C. oil bath overnight. The reaction mixture was diluted with EtOAc (60 mL) and washed with brine (25 mL). The aqueous phase was back-extracted with EtOAc (50 mL). The combined organic layers were washed with brine (25 mL), dried (MgSO4), concentrated in vacuo and purified by chromatography to afford 4-(4-amino-3-fluorophenoxy)picolinonitrile (0.162 g, 31% yield) as a colorless oil. 1H NMR (DMSO-d6) δ 8.56 (d, J=5.6 Hz, 1H), 7.62 (d, J=2.0 Hz, 1H), 7.14 (dd, J=6.0, 2.8 Hz, 1H), 7.03 (dd, J=11.6, 2.4 Hz, 1H), 6.88-6.77 (m, 2H), 5.25 (s, 2H); MS (ESI) m/z: 230.0 (M+H+).

Workup

  1. customThe resultant solution was de-gassed in vacuo
  2. customquickly capped
  3. customthe vial was de-gassed again
  4. temperatureheated in a 90° C. oil bath overnight
  5. additionThe reaction mixture was diluted with EtOAc (60 mL)
  6. washwashed with brine (25 mL)
  7. extractionThe aqueous phase was back-extracted with EtOAc (50 mL)
  8. washThe combined organic layers were washed with brine (25 mL)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. custompurified by chromatography

Sources & evidence

ORD record
ord-ca49a737a7af4d02b414559bcc9207b4
Source dataset
uspto-grants-2010_09
Patent number
US07790756B2

Reaction notes

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