Hydrochloric Acid → HCID 66585038, compound

HRID 589883Notes

Reaction equation

HRID 589883 reaction equation
C(O[C:6]([NH:8][CH2:9][CH2:10][N:11]1[C:15](Br)=[C:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=2)[C:13]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:12]1)=O)(C)(C)C.[ClH:29].C=O.[OH-].[Na+]>C(O)C>[Cl:29][C:15]1[N:11]2[CH2:10][CH2:9][NH:8][CH2:6][C:12]2=[C:13]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:14]=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 66584135HCID 66584135, compound

Product 1

HCID 66585038HCID 66585038, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 38.4 g (84.3 mmol) of ethyl 1-(2-tert-butoxycarbonylaminoethyl)-5-bromo-4-(3-fluorophenyl)-1H-pyrrole-3-carboxylate in 80 ml of ethanol are added slowly 271 ml (949 mmol) of aqueous 3.5N hydrochloric acid solution. The formation of a white precipitate is rapidly observed and then, after 45 minutes, the medium becomes clear, while the mixture is heated to 70° C., and 3.00 g (31.2 mmol) of paraformaldehyde are added. Heating is continued at 70° C. for 1 hour. After cooling, the reaction medium is poured into a mixture of ice and 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 330 g of silica gel, eluting with a mixture of 3% methanol in dichloromethane, to give 14.3 g of ethyl 6-chloro-7-(3-fluorophenyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-8-carboxylate after crystallizing from 50 ml of diisopropyl ether.

Workup

  1. temperatureHeating
  2. waitis continued at 70° C. for 1 hour
  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 330 g of silica gel
  9. washeluting with a mixture of 3% methanol in dichloromethane

Sources & evidence

ORD record
ord-ff3e693cf75e4a11bd3da716d1c37a11
Source dataset
uspto-grants-2016_01
Patent number
US09233965B2

Reaction notes

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