Hydrochloric Acid → HCID 66584715, compound

HRID 1629980Notes

Reaction equation

HRID 1629980 reaction equation
C(O[C:6](=O)[NH:7][CH2:8][CH2:9][N:10]1[CH:14]=[C:13]([C:15]#[N:16])[C:12]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)=[C:11]1[Cl:24])(C)(C)C.Cl.C=O.[OH-].[Na+]>C(O)C>[Cl:24][C:11]1[N:10]2[CH2:9][CH2:8][NH:7][CH2:6][C:14]2=[C:13]([C:15]#[N:16])[C:12]=1[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 66585012HCID 66585012, compound

Product 1

HCID 66584715HCID 66584715, compoundYield 58.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 47.3 g (130 mmol) of tert-butyl{2-[2-chloro-4-cyano-3-(3-fluorophenyl)-1H-pyrrol-1-yl]ethyl}-carbamate in 85 ml of ethanol are added slowly 488 ml (1465 mmol) of aqueous 3N hydrochloric acid solution. Setting to a solid is rapidly observed, and the medium then becomes clear. After 45 minutes, 5.56 g (48.1 mmol) of paraformaldehyde are added and heating is continued at 70° C. for 2 hours 30 minutes. After cooling, the reaction medium is poured slowly into ice-cold aqueous 4N sodium hydroxide solution. The product is extracted with dichloromethane, the organic phase is dried over sodium sulfate and the solvent is evaporated off under reduced pressure to give a brown oil, which is chromatographed on a column of 300 g of silica gel, eluting with a mixture of 1 to 2% methanol in dichloromethane, to give 21.0 g of 6-chloro-7-(3-fluorophenyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carbonitrile in the form of a beige-coloured powder after triturating in 150 ml of diisopropyl ether, at reflux, chilling, filtering off and drying.

Workup

  1. temperatureheating
  2. waitis continued at 70° C. for 2 hours 30 minutes
  3. temperatureAfter cooling
  4. extractionThe product is extracted with dichloromethane
  5. dry with materialthe organic phase is dried over sodium sulfate
  6. customthe solvent is evaporated off under reduced pressure
  7. customto give a brown oil, which
  8. customis chromatographed on a column of 300 g of silica gel
  9. washeluting with a mixture of 1 to 2% methanol in dichloromethane

Sources & evidence

ORD record
ord-841d5034c34a4a1ca88ebac0b90e6811
Source dataset
uspto-grants-2014_07
Patent number
US08791119B2

Reaction notes

Loading…