Dimethylformamide → Tert-butyl 3-carbamoylpiperazine-1-carboxylate

HRID 874966Notes

Reaction equation

HRID 874966 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH:9]1[C:21]([OH:23])=O)=O)(C)(C)C.C[N:25](C=O)C.S(Cl)(Cl)=O>C1COCC1.N1C=CC=CC=1>[C:21]([CH:9]1[NH:8][CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])[CH2:10]1)(=[O:23])[NH2:25]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 112559791,4-Di-Boc-piperazine-2-carboxylic acid

Product 1

HCID 11042527Tert-butyl 3-carbamoylpiperazine-1-carboxylateYield 49%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

1,4-Bis(tert-butoxycarbonyl)piperazine-2-carboxylic acid (1.0 g, 3.03 mmol) was suspended in THF (5 mL) and pyridine (0.36 mL), DMF (0.1 mL) was added, followed by thionyl chloride (0.23 mL, 3.03 mmol). The reaction mixture was stirred at 40° C. for 4 h and then concentrated under reduced pressure. The crude product was dissolved in CH2Cl2 and transferred to a sealed tube. A saturated solution of ammonia in dioxane (10 mL) was added to the compound and the resulting reaction mixture was stirred at 40° C. for 2 h followed by room temperature stirring for 12 h. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in 1.5 N HCl. The aqueous layer was washed with diethyl ether and then basified with 1N sodium hydroxide solution. The organic product was extracted with CH2Cl2. The combined extracts were dried over anhydrous sodium sulfate, and concentrated under reduced pressure to get tert-butyl 3-carbamoylpiperazine-1-carboxylate (340 mg, yield 49%), which was carried through without further purification. 1H NMR (400 MHz, CDCl3) δ 6.70 (br s, 1H), 5.51 (br s, 1H), 4.06-4.03 (m, 1H), 3.77 (m, 1H), 3.37-3.33 (m, 1H), 3.11-2.95 (m, 3H), 2.81-2.76 (m, 1H), 1.47 (s, 9H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe crude product was dissolved in CH2Cl2
  3. customtransferred to a sealed tube
  4. additionA saturated solution of ammonia in dioxane (10 mL) was added to the compound
  5. customthe resulting reaction mixture
  6. stirringwas stirred at 40° C. for 2 h
  7. customfollowed by room temperature
  8. stirringstirring for 12 h
  9. concentrationThe reaction mixture was concentrated under reduced pressure
  10. dissolutionthe residue was dissolved in 1.5 N HCl
  11. washThe aqueous layer was washed with diethyl ether
  12. extractionThe organic product was extracted with CH2Cl2
  13. dry with materialThe combined extracts were dried over anhydrous sodium sulfate
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9937423d53ce42d2bfa04888e9b6e274
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

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