Triethylamine → Tert-butyl 4-(tetrazolo[1,5-a]pyrazin-8-yl)piperazine-1-carboxylate

HRID 1045732Notes

Reaction equation

HRID 1045732 reaction equation
Cl[C:2]1[C:3]2[N:4]([N:8]=[N:9][N:10]=2)[CH:5]=[CH:6][N:7]=1.[N:11]1([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.C(N(CC)CC)C>CCO>[N:10]1[N:9]=[N:8][N:4]2[CH:5]=[CH:6][N:7]=[C:2]([N:14]3[CH2:13][CH2:12][N:11]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16][CH2:15]3)[C:3]=12

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 126931908-Chlorotetrazolo[1,5-a]pyrazine

Product 1

HCID 58447015Tert-butyl 4-(tetrazolo[1,5-a]pyrazin-8-yl)piperazine-1-carboxylateYield 91%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A 3 L round bottom flask was charged with 8-chlorotetrazolo[1,5-a]pyrazine (350 g, 2.3 mol), tert-butyl piperazine-1-carboxylate (420 g, 2.3 mol), triethylamine (460 g, 4.5 mol), and EtOH (2 L). The mixture was heated at reflux for 1 h. Work-up: the reaction mixture was concentrated in vacuo. The residue was mixed with saturated aqueous NaHCO3 (1 L) and then extracted with CH2Cl2 (1 L×3). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was further purified by flash column chromatography on silica gel with 8% EtOAc in CH2Cl2 (containing 2% Et3N), to afford 630 g (91%) of the product as a white solid. MS m/z: 306 (M+H+).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 1 h
  3. concentrationthe reaction mixture was concentrated in vacuo
  4. additionThe residue was mixed with saturated aqueous NaHCO3 (1 L)
  5. extractionextracted with CH2Cl2 (1 L×3)
  6. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was further purified by flash column chromatography on silica gel with 8% EtOAc in CH2Cl2 (containing 2% Et3N)

Sources & evidence

ORD record
ord-73352dacd55a451bb0e8e21c2302e3f6
Source dataset
uspto-grants-2013_10
Patent number
US08569300B2

Reaction notes

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