Sodium Hydroxide → tert-Butyl 4-cyclopropylpiperazine-1-carboxylate

HRID 13558Notes

Reaction equation

HRID 13558 reaction equation
[N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C(O[C:17]1(O[Si](C)(C)C)[CH2:19][CH2:18]1)C.[BH3-]C#N.[Na+].[OH-].[Na+]>O.C(O)(=O)C.CO.C1COCC1>[CH:17]1([N:4]2[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]2)[CH2:19][CH2:18]1

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydride

Product 1

HCID 20294524tert-Butyl 4-cyclopropylpiperazine-1-carboxylate

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of tert-butyl piperazine-1-carboxylate (75.0 g), THF (500 mL), methanol (500 mL), [(1-ethoxycyclopropyl)oxy]trimethylsilane (161 mL), NaBH3CN (38.0 g), and acetic acid (37 mL) was heated at 60° C. for 5 h. The mixture was cooled to room temperature, treated with water (30 mL) and stirred for 5 min. The mixture was then treated with 1 N NaOH (130 mL) and was further stirred for 15 min. The mixture was concentrated, and the remaining aqueous solution was extracted with CH2Cl2 (500 mL). The organic layer was washed with 1 N NaOH (500 mL). The combined aqueous layers were extracted with CH2Cl2 (150 mL). The combined organic layers were washed with brine (400 mL), dried (Na2SO4), and concentrated to yield the title compound as a white solid.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. stirringwas further stirred for 15 min
  3. concentrationThe mixture was concentrated
  4. extractionthe remaining aqueous solution was extracted with CH2Cl2 (500 mL)
  5. washThe organic layer was washed with 1 N NaOH (500 mL)
  6. extractionThe combined aqueous layers were extracted with CH2Cl2 (150 mL)
  7. washThe combined organic layers were washed with brine (400 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-db7dbad0b7b94f2588869652ef25d01f
Source dataset
uspto-grants-2010_06
Patent number
US07728129B2

Reaction notes

Loading…