Hydrochloric Acid → 4-(5-chloro-2-oxo-4-(piperidin-4-yloxy)pyridin-1(2H)-yl)-2-fluorobenzonitrile

HRID 1518494Notes

Reaction equation

HRID 1518494 reaction equation
[Cl:1][C:2]1[C:3]([O:18][CH:19]2[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]2)=[CH:4][C:5](=[O:17])[N:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]#[N:15])=[C:10]([F:16])[CH:9]=2)[CH:7]=1.Cl>CO>[Cl:1][C:2]1[C:3]([O:18][CH:19]2[CH2:20][CH2:21][NH:22][CH2:23][CH2:24]2)=[CH:4][C:5](=[O:17])[N:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]#[N:15])=[C:10]([F:16])[CH:9]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 57468467Tert-butyl 4-(5-chloro-1-(4-cyano-3-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate

Product 1

HCID 673687134-(5-chloro-2-oxo-4-(piperidin-4-yloxy)pyridin-1(2H)-yl)-2-fluorobenzonitrileYield 68.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A suspension of tert-butyl 4-(5-chloro-1-(4-cyano-3-fluorophenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (2.2 g, 4.18 mmol) in MeOH (15 mL) was added hydrogen chloride (4M in 1,4-dioxane) (0.609 g, 16.70 mmol) and stirred at rt. After 6 h stirring, solvent MeOH was evaporated and the resulting crude was diluted with EtOAc (50 mL). After saturated aqueous NaHCO3 was added to adjust PH>7, the resulting mixture was vigorously stirred for 2 h. The organic layers was collected and the aqueous layer was back-extracted with EtOAc 2×. The combined extracts were dried (Na2SO4) and evaporated under reduced pressure to give a brown solid as a crude product (1 g, 2.88 mmol). MS (ESI) 348 (M+H).

Workup

  1. stirringAfter 6 h stirring
  2. customsolvent MeOH was evaporated
  3. additionthe resulting crude was diluted with EtOAc (50 mL)
  4. additionAfter saturated aqueous NaHCO3 was added
  5. stirringthe resulting mixture was vigorously stirred for 2 h
  6. customThe organic layers was collected
  7. extractionthe aqueous layer was back-extracted with EtOAc 2×
  8. dry with materialThe combined extracts were dried (Na2SO4)
  9. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-25d16bae3c3d48cfb529dad7f5d1bdd3
Source dataset
uspto-grants-2012_07
Patent number
US08232404B2

Reaction notes

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