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

HRID 1676225Notes

Reaction equation

HRID 1676225 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. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-47f17802e0a44436918afecc2e013b1f
Source dataset
uspto-grants-2011_08
Patent number
US08003796B2

Reaction notes

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