Hydrochloric Acid → Tert-butyl 4-(4-nitrobenzoyl)piperazine-1-carboxylate

HRID 2410710Notes

Reaction equation

HRID 2410710 reaction equation
[N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8](Cl)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].N1C=CC=CC=1.[N:19]1([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1.Cl>C(OCC)(=O)C.ClCCl>[N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8]([N:22]2[CH2:21][CH2:20][N:19]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:24][CH2:23]2)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 85024-Nitrobenzoyl chlorideHCID 143452tert-Butyl piperazine-1-carboxylate

Product 1

HCID 2764459Tert-butyl 4-(4-nitrobenzoyl)piperazine-1-carboxylateYield 71.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A 500 ml round bottom flask was loaded with 4-nitrobenzoyl chloride (10.2 g, 53.9 mmol) and dichloromethane (100 ml) and cooled to 0° C. Pyridine (10 ml, 124 mmol) was added, followed by tert-butyl piperazine-1-carboxylate (10.2 g, 54.8 mmol) (solid, in portions) while stirring at 0° C. After the addition was completed, the ice bath was removed and the reaction mixture stirred while allowing the reaction to warm to room temperature overnight. The mixture was poured into a separating funnel loaded with 250 ml ethyl acetate and 250 ml 1N aq. HCl. The layers were separated, the organic layer washed one more time with 1 M aq. HCl, then with sat. aq. NaHCO3 solution (2×), then brine (1×), then dried over MgSO4, filtered and concentrated in vacuum. 12.9 g tert-butyl 4-(4-nitrobenzoyl)piperazine-1-carboxylate were isolated as a white solid. MS (ESI) m/z 280 (M+H—C4H8), 236 (M+H-BOC). 1H NMR (CDCl3) δ ppm 8.28 (d, 2H, J=8.6), 7.57 (d, 2H, J=8.6), 3.76 (bs, 2H), 3.53 (bs, 2H), 3.39 (bs, 2H), 3.33 (bs, 2H), 1.46 (s, 9H).

Workup

  1. additionAfter the addition
  2. customthe ice bath was removed
  3. stirringthe reaction mixture stirred
  4. customthe reaction
  5. temperatureto warm to room temperature overnight
  6. additionThe mixture was poured into a separating funnel
  7. customThe layers were separated
  8. washthe organic layer washed one more time with 1 M aq. HCl
  9. dry with materialwith sat. aq. NaHCO3 solution (2×), then brine (1×), then dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-bd1665b9960b46f1ad1d2dbfbff1b8b2
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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