Sodium Carbonate → HCID 69095725, compound

HRID 594412Notes

Reaction equation

HRID 594412 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH:11]1[N:16]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=2)[C:15](=[O:29])[CH2:14][N:13]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:12]1=O.[BH4-].[Na+].[BH3-]C#N.[Na+].C([O-])([O-])=O.[Na+].[Na+]>CO.C(Cl)Cl>[CH3:10][O:9][C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[C:4]=1[CH:11]1[N:16]([CH2:17][C:18]2[CH:19]=[CH:20][C:21]([O:24][C:25]([F:28])([F:26])[F:27])=[CH:22][CH:23]=2)[C:15](=[O:29])[CH2:14][N:13]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:12]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 4311764Sodium borohydrideHCID 5003444Sodium cyanoborohydrideHCID 86695635HCID 86695635, compound

Product 1

HCID 69095725HCID 69095725, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A cooled (0° C.) solution of tert-butyl 3-(2,6-dimethoxyphenyl)-2,5-dioxo-4-(4-(trifluoromethoxy)benzyl)piperazine-1-carboxylate (718 mg; 1.36 mmol) in anh. MeOH (15 ml) was treated with NaBH4 (221 mg; 5.47 mmol), and stirring at 0° C., under nitrogen, was continued for 30 min. After concentration to dryness under reduced pressure, the residue was dissolved in AcOEt, and washed successively with 1 M aq. HCl and brine. The separated aq. layer was further extracted with AcOEt (3×10 ml), and the mixed organic layers were dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Acetic acid (20 ml) was added, and the cooled (0° C.) mixture was then treated portionwise with NaBH3CN (516 mg; 8.21 mmol). The resulting mixture was further stirred at rt, under nitrogen, for 1 h. DCM and aq. sat. Na2CO3 were then added, and the separated aq. layer was further extracted with DCM. The mixed organic layers were then dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Purification by FC (DCM/MeOH=25/1) afforded tert-butyl 3-(2,6-dimethoxyphenyl)-5-oxo-4-(4-(trifluoromethoxy)benzyl)piperazine-1-carboxylate as an orange oil. LC-MS (conditions D): tR=1.12 min.; [M+H]+: 511.01 g/mol.

Workup

  1. concentrationAfter concentration to dryness under reduced pressure
  2. dissolutionthe residue was dissolved in AcOEt
  3. washwashed successively with 1 M aq. HCl and brine
  4. extractionThe separated aq. layer was further extracted with AcOEt (3×10 ml)
  5. dry with materialthe mixed organic layers were dried over anh. MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure
  8. additionAcetic acid (20 ml) was added
  9. temperaturethe cooled (0° C.) mixture
  10. stirringThe resulting mixture was further stirred at rt, under nitrogen, for 1 h
  11. extractionthe separated aq. layer was further extracted with DCM
  12. dry with materialThe mixed organic layers were then dried over anh. MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated to dryness under reduced pressure
  15. customPurification by FC (DCM/MeOH=25/1)

Sources & evidence

ORD record
ord-c5c650c28ef24d56a4365749ef80665b
Source dataset
uspto-grants-2016_01
Patent number
US09242970B2

Reaction notes

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