Tetrahydrofuran → HCID 86751262, compound

HRID 1378940Notes

Reaction equation

HRID 1378940 reaction equation
C([Li])CCC.[N:6]1[CH:11]=[CH:10][N:9]=[CH:8][CH:7]=1.[F:12][C:13]1[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[C:14]=1[CH:15]=O.[NH4+].[Cl-].C1C[O:27]CC1>C(Cl)Cl>[OH:27][C:14]1([C:17]([Cl:21])=[CH:18][CH:19]=[CH:20][CH:13]1[F:12])[CH2:15][C:7]1[CH:8]=[N:9][CH:10]=[CH:11][N:6]=1

Participants

7

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 9261PyrazineHCID 25517Ammonium ChlorideHCID 678472-Chloro-6-fluorobenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 86751262HCID 86751262, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-70 °C

Procedure

35 ml of a 2.5M solution of butyl lithium were added to 14 ml of TMP in 35 ml THF over a period of 10 minutes at a temperature of -70° C. After stirring at -70° C. for 10 minutes, the reaction mixture was allowed to warm up to 0° C. and kept at 0° C. for 10 minutes. The reaction mixture was then cooled to -70° C. again and a solution of 5.0 g of pyrazine in 25 ml THF was then added over a period of 15-20 minutes, while maintaining the temperature below -60° C. The reaction mixture was then stirred at -70° C. for one hour. 10.4 g of 2-fluoro-6-chlorobenzaldehyde were added, while keeping the temperature below -60° C. and the resulting reaction mixture was then stirred at -70° C. for about two hours. The reaction mixture was allowed to warm slowly to room temperature and stirred overnight. 45 ml of saturated NH4Cl were added to the reaction mixture. Then, 150 ml of methylene chloride were added and the layers were separated. The methylene chloride layer was washed with brine, dried (MgSO4), filtered and stripped to a dark brown residue. The residue was put on a silica gel column and eluted with a 4:1 mixture of hexane:diethyl ether, then 2:1 hexane:diethyl ether. The desired fraction yielded 2.0 g of 2-(1-hydroxy-2'-fluoro-6'-chlorobenzyl) pyrazine in a yellow, semi-solid form.

Workup

  1. temperatureto warm up to 0° C.
  2. waitkept at 0° C. for 10 minutes
  3. temperatureThe reaction mixture was then cooled to -70° C. again
  4. temperaturewhile maintaining the temperature below -60° C
  5. stirringThe reaction mixture was then stirred at -70° C. for one hour
  6. customthe temperature below -60° C.
  7. customthe resulting reaction mixture
  8. stirringwas then stirred at -70° C. for about two hours
  9. temperatureto warm slowly to room temperature
  10. stirringstirred overnight
  11. customthe layers were separated
  12. washThe methylene chloride layer was washed with brine
  13. dry with materialdried (MgSO4)
  14. filtrationfiltered
  15. washeluted with a 4:1 mixture of hexane

Sources & evidence

ORD record
ord-ee618a9436bc41069c46a75d4891207c
Source dataset
uspto-grants-1997_09
Patent number
US05670453

Reaction notes

Loading…