Triethylamine → tert-Butyl 4-cyanopiperazine-1-carboxylate

HRID 2199683Notes

Reaction equation

HRID 2199683 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.[CH2:14]([N:16](CC)CC)C.N#CBr>C1COCC1>[C:14]([N:4]1[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]1)#[N:16]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10476Cyanogen BromideHCID 143452tert-Butyl piperazine-1-carboxylate

Product 1

HCID 14068968tert-Butyl 4-cyanopiperazine-1-carboxylateYield 86.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

1,1-Dimethylethyl 1-piperazinecarboxylate (25 g, 134.2 mmol) was taken into THF (100 mL) followed by addition of triethylamine (25 mL, 178 mmol). The solution was cooled to 0° C. followed by addition dropwise addition of cyanogen bromide (15.6 g, 147.6 mmol) in THF (100 mL) and the resulting mixture was allowed to warm to room temperature then stirred an additional 12 hours. The reaction mixture was concentrated in vacuo and partitioned with ethyl ether and water. The organic layer was washed once with saturated aqueous NaCl then dried over anhydrous magnesium sulfate followed by concentration to afford 1,1-dimethylethyl 4-cyanopiperazine-1-carboxylate (24.5 g, 86% yield) as a colorless crystalline solid. 1H-NMR (400 MHz, CDCl3): 3.51 (tr, 4H), 3.19 (tr, 4H), 1.46 (s, 9H).

Workup

  1. temperatureto warm to room temperature
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. custompartitioned with ethyl ether and water
  4. washThe organic layer was washed once with saturated aqueous NaCl
  5. dry with materialthen dried over anhydrous magnesium sulfate
  6. concentrationfollowed by concentration

Sources & evidence

ORD record
ord-a15e75b2a24b450b8960c549383278b4
Source dataset
uspto-grants-2016_06
Patent number
US09359332B2

Reaction notes

Loading…