Formaldehyde → HCID 19994583, compound

HRID 2248594Notes

Reaction equation

HRID 2248594 reaction equation
[CH2:1]=O.Cl.[CH3:4][NH:5][CH3:6].[C:7]1([CH2:13][CH2:14][C:15]2[C:16]3[N:17]([CH:21]=[CH:22][CH:23]=3)[CH:18]=[CH:19][N:20]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[OH-].[Na+]>CC#N>[CH2:12]([C:7]1[CH:13]=[C:14]([C:15]2[C:16]3[N:17]([C:21]([CH2:4][N:5]([CH3:1])[CH3:6])=[CH:22][CH:23]=3)[CH:18]=[CH:19][N:20]=2)[CH:10]=[CH:9][CH:8]=1)[CH3:11]

Participants

6

Reactant 4

HCID 712Formaldehyde3×HCID 10473Dimethylamine, hydrochloride2×HCID 14798Sodium HydroxideHCID 15662071HCID 15662071, compound

Product 1

HCID 19994583HCID 19994583, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
-78 °C

Procedure

A 500 mL round bottom flask was half-filled with paraformaldehyde (~200 g) and then connected by means of a rubber hose to an acetone-dry ice trap. The trap was fitted with a 100 mL round bottom flask that contained dry dimethylamine hydrochloride (880 mg, 18 mmol. 1.2 eq. with respect to 1-(2-phenylethyl)pyrrolo[1,2-a]pyrazine). The flask containing the dimethylamine hydrochloride was then cooled to -78° C. and the flask containing the paraformaldehyde was heated between 180°-200° C. until an excess of paraformaldehyde had been distilled. The reaction mixture was then allowed to warm to room temperature. The solid mixture was cooled again to -20° C. and a solution of 1-(2-phenylethyl)pyrrolo[1,2-a]pyrazine (2 g., 9 mmol) in 20 mL of dry CH3CN was added. The reaction mixture was allowed to reach room temperature and left stirring at this temperature for 8 hours. A solution of NaOH (5M, 40 mL) was then added. The resulting solution was extracted with ethyl acetate (3×30 mL). The organic extracts were extracted with a solution of HCl (0.1M, 50 mL). The aqueous acid phase was then separated, neutralized with a solution of NaOH (2M, 50 mL) and extracted with ethyl acetate (2×50 mL). The organic extracts were combined, dried over MgSO4 and evaporated to give 1.8 g (73%) of the title compound,

Workup

  1. customconnected by means of a rubber hose to an acetone-dry ice trap
  2. customThe trap was fitted with a 100 mL round bottom flask that
  3. distillationhad been distilled
  4. temperatureto warm to room temperature
  5. temperatureThe solid mixture was cooled again to -20° C.
  6. customto reach room temperature
  7. waitleft
  8. extractionThe resulting solution was extracted with ethyl acetate (3×30 mL)
  9. extractionThe organic extracts were extracted with a solution of HCl (0.1M, 50 mL)
  10. customThe aqueous acid phase was then separated
  11. extractionextracted with ethyl acetate (2×50 mL)
  12. dry with materialdried over MgSO4
  13. customevaporated

Sources & evidence

ORD record
ord-709a201e57814a6ab05c31a461a0e77e
Source dataset
uspto-grants-1991_08
Patent number
US05041442

Reaction notes

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