2,6-Lutidine → HCID 59846103, compound

HRID 549929Notes

Reaction equation

HRID 549929 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([C@H:17]3[CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19][N:18]3[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[O:16])[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].N1C(C)=CC=CC=1C.[Si](OS(C(F)(F)F)(=O)=O)(C(C)(C)C)(C)C>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:10][CH2:11][N:12]([C:15]([C@H:17]3[CH2:22][NH:21][CH2:20][CH2:19][N:18]3[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[O:16])[CH2:13][CH2:14]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 59846036HCID 59846036, compound

Product 1

HCID 59846103HCID 59846103, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of di-tert-butyl (2R)-2-{[4-(3,4-dichlorophenyl)piperazin-1-yl]carbonyl}piperazine-1,4-dicarboxylate and 2,6-lutidine in dichloromethane at ice bath temperature under argon was added TBDMSOTf (total of 0.4 mL added following the reaction by tlc and lc-ms until complete. The ice-bath was removed and the reaction quenched with saturated aqueous ammonium chloride at ambient temperature. The mixture was partitioned between water and dichloromethane and the organic layer washed with brine and concentrated at reduced pressure. The residue was dissolved in THF and cooled to ice bath temperature. Water (0.5 mL) was added, followed by TBAF (1M in THF) drop-wise. The mixture was again warmed to ambient temperature and partitioned between dichloromethane and water. The organic phase was dried (MgSO4), filtered and concentrated. The residue (647 mg) was purified by silica gel chromatography on an Isco Companion (40 g column), eluting with 0-10% methanol in dichloromethane to give the title intermediate (204 mg). A further amount of impure compound (48 mg) was also isolated.

Workup

  1. additionadded
  2. customthe reaction by tlc and lc-ms until complete
  3. customThe ice-bath was removed
  4. customthe reaction quenched with saturated aqueous ammonium chloride at ambient temperature
  5. customThe mixture was partitioned between water and dichloromethane
  6. washthe organic layer washed with brine
  7. concentrationconcentrated at reduced pressure
  8. dissolutionThe residue was dissolved in THF
  9. temperaturecooled to ice bath temperature
  10. additionWater (0.5 mL) was added
  11. custompartitioned between dichloromethane and water
  12. dry with materialThe organic phase was dried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe residue (647 mg) was purified by silica gel chromatography on an Isco Companion (40 g column)
  16. washeluting with 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-19b14111b36a46af8f8c66d039914d3d
Source dataset
uspto-grants-2011_05
Patent number
US07943768B2

Reaction notes

Loading…