Hydrochloric Acid → HCID 178517913, compound

HRID 1593584Notes

Reaction equation

HRID 1593584 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([O:16]CC)=O)[C:10](=O)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(=O)C.[CH:24]([NH2:26])=[NH:25].CC[O-].[Na+].Cl>C(N1CCC(C(OCC)=O)C(=O)C1)C1C=CC=CC=1.CO.C(Cl)Cl.CCO>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]2[C:14]([OH:16])=[N:26][CH:24]=[N:25][C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 160693Formamidine acetateHCID 419705Ethyl 3-oxo-1-(phenylmethyl)-4-piperidinecarboxylateHCID 2723922Sodium ethoxide

Product 1

HCID 178517913HCID 178517913, compoundYield 180.5%

Reagents, catalysts & solvents 4

HCID 419705Ethyl 3-oxo-1-(phenylmethyl)-4-piperidinecarboxylateCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Ethyl 1-benzyl-3-oxopiperidine-4-carboxylate (30 g, 101 mmol) was combined with formamidine aceate (10.5 g, 101 mmol) and EtOH (450 mL) in a 2-liter flask. The resulting mixture was stirred at 0° C. and treated with NaOEt (21% in EtOH) (112.6 mL, 299 mmol). The reaction was heated at 60° C. overnight and monitored for completion via 1 cms and TLC (DCM:MeOH:: 95:5). Additional ethyl 1-benzyl-3-oxopiperidine-4-carboxylate (2 g, 6.6 mmol) was added after 12 h with continued heating at 60° C. The reaction was complete after 4 h as indicated by LCMS. The cooled reaction was reduced in vacuo and the residue was treated concentrated HCl (300 mL) and stirred overnight at room temperature. The solvents were removed under vacuum and the resulting solids treated with EtOH (300 mL), stirred for 15 minutes, and then filtered. The mother liquor was discarded and the precipitate dried in a vacuum oven affording 7-benzyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-ol (44 g) as the tri-HCl salt which was used directly in the next step.

Workup

  1. temperatureThe reaction was heated at 60° C. overnight
  2. temperaturewith continued heating at 60° C
  3. customThe cooled reaction
  4. stirringstirred overnight at room temperature
  5. customThe solvents were removed under vacuum
  6. additionthe resulting solids treated with EtOH (300 mL)
  7. stirringstirred for 15 minutes
  8. filtrationfiltered
  9. customthe precipitate dried in a vacuum oven

Sources & evidence

ORD record
ord-382767e8cc46452b8a0640c57e4c3d75
Source dataset
uspto-grants-2007_11
Patent number
US07297700B2

Reaction notes

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