Nitrogen → Tert-butyl 4-(3-(aminomethyl)-4-chlorobenzyl)piperazine-1-carboxylate

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.

1. customTo a 250 mL round-bottom flask fitted with a reflux condenser
2. temperatureThis mixture was cooled in an ice bath
3. additionadded dropwise to the reaction mixture via syringe
4. customThe ice bath was removed
5. temperaturethe reaction mixture was heated
6. temperatureat reflux for 20 h
7. additionwas added 48 mL of 20% HOAc in water (v/v)
8. concentrationThe mixture was concentrated to half its original volume with a rotary evaporator
9. additiondiluted with 20 mL of 10% citric acid
10. washThis mixture was washed once with 25 mL of EtOAc
11. additionthe aqueous layer was brought to pH=11 by the addition of 52 mL of 3N NaOH
12. extractionThe resultant mixture was extracted with EtOAc (3×40 mL)
13. washThe combined extracts were washed with 40 mL of saturated NaCl solution
14. dry with materialThe organic layer was dried over Na2SO4
15. filtrationfiltered
16. concentrationconcentrated

ORD record

ord-4185a0f04b3d44c5af1d9e2bc7551c9a

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07825120B2