Reaction #1256774

Reaction equation

EDC

HOBT

triethylamine

4-chloro-3-cyanobenzoic acid

1-(tert-butoxycarbonyl)piperazine

EDC

HOBT

Triethylamine

→

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

Yield 96.2%

Solvents

CH2Cl2

Conditions

Workup

1. 1
   workup.STIRRINGAfter stirring for an additional 20 h the reaction mixture
2. 2
   Washwas washed with 6 mL portions of: 10% KHSO4, water, saturated NaHCO3, and saturated NaCl
3. 3
   DryingThe organic extracts were dried over Na2SO4
4. 4
   Filtrationfiltered
5. 5
   Concentrationconcentrated

Procedure

In a 100 mL round-bottom flask under a positive nitrogen pressure of 4-chloro-3-cyanobenzoic acid (4.28 mmol), 1-(tert-butoxycarbonyl)piperazine (1.59 g, 8.56.mmol), EDC (903 mg, 4.71 mmol) and HOBT (694 mg, 5.14 mmol) were dissolved in 17 mL of CH2Cl2. Triethylamine (1.5 mL, 10.7 mmol) was added and the reaction mixture was stirred for 20 h. After this time additional quantities of EDC (411 mg, 2.14 mmol), HOBT (290 mg, 2.14 mmol) and triethylamine (300 □L, 2.14 mmol) were added. After stirring for an additional 20 h the reaction mixture was washed with 6 mL portions of: 10% KHSO4, water, saturated NaHCO3, and saturated NaCl. The organic extracts were dried over Na2SO4, filtered and concentrated to afford 1.44 g of tert-butyl 4-(4-chloro-3-cyanobenzoyl)piperazine-1-carboxylate as a beige solid.

Source