Reaction #1256775

Reaction equation

N2

tert-butyl 4-(4-chloro-3-cyanobenzoyl)piperazine-1-carboxylate

→

tert-butyl 4-(3-(aminomethyl)-4-chlorobenzyl)piperazine-1-carboxylate

Yield 71.4%

Solvents

THF

THF

Conditions

Workup

1. 1
   OtherTo a 250 mL round-bottom flask fitted with a reflux condenser
2. 2
   TemperatureThis mixture was cooled in an ice bath
3. 3
   workup.ADDITIONadded dropwise to the reaction mixture via syringe
4. 4
   OtherThe ice bath was removed
5. 5
   Temperaturethe reaction mixture was heated
6. 6
   Temperatureat reflux for 20 h
7. 7
   workup.ADDITIONwas added 48 mL of 20% HOAc in water (v/v)
8. 8
   ConcentrationThe mixture was concentrated to half its original volume with a rotary evaporator
9. 9
   workup.ADDITIONdiluted with 20 mL of 10% citric acid
10. 10
    WashThis mixture was washed once with 25 mL of EtOAc
11. 11
    workup.ADDITIONthe aqueous layer was brought to pH=11 by the addition of 52 mL of 3N NaOH
12. 12
    ExtractionThe resultant mixture was extracted with EtOAc (3×40 mL)
13. 13
    WashThe combined extracts were washed with 40 mL of saturated NaCl solution
14. 14
    DryingThe organic layer was dried over Na2SO4
15. 15
    Filtrationfiltered
16. 16
    Concentrationconcentrated

Procedure

To a 250 mL round-bottom flask fitted with a reflux condenser, rubber septum and stir bar under a positive pressure of N2 was added 10.3 mL of 1M BH3.THF complex in THF. This mixture was cooled in an ice bath. The tert-butyl 4-(4-chloro-3-cyanobenzoyl)piperazine-1-carboxylate (1.44 g, 4.12 mmol) was dissolved in 20 mL of THF and added dropwise to the reaction mixture via syringe. The ice bath was removed, replaced with a heating mantle and the reaction mixture was heated at reflux for 20 h. The reaction was cooled to RT and to the mixture was added 48 mL of 20% HOAc in water (v/v) and the mixture was stirred between pH 3-4 for 20 h. The mixture was concentrated to half its original volume with a rotary evaporator and then diluted with 20 mL of 10% citric acid. This mixture was washed once with 25 mL of EtOAc and the aqueous layer was brought to pH=11 by the addition of 52 mL of 3N NaOH. The resultant mixture was extracted with EtOAc (3×40 mL). The combined extracts were washed with 40 mL of saturated NaCl solution. The organic layer was dried over Na2SO4, filtered and concentrated to give 1.00 g of tert-butyl 4-(3-(aminomethyl)-4-chlorobenzyl)piperazine-1-carboxylate as a pale yellow oil.

Source