Hydrochloric Acid → (1S,4S)-2,5-Diazabicyclo[2.2.1]heptane-2-carboxamide hydrochloride

HRID 547347Notes

Reaction equation

HRID 547347 reaction equation
C([O:5][C:6]([N:8]1[CH2:13][C@@H:12]2[CH2:14][C@H:9]1[CH2:10][NH:11]2)=O)(C)(C)C.C[Si]([N:19]=C=O)(C)C.[ClH:22]>C(Cl)Cl>[ClH:22].[C@H:9]12[CH2:14][C@H:12]([NH:11][CH2:10]1)[CH2:13][N:8]2[C:6]([NH2:19])=[O:5]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 70696Trimethylsilyl isocyanateHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptane

Product 1

HCID 57464029(1S,4S)-2,5-Diazabicyclo[2.2.1]heptane-2-carboxamide hydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl-(S,S)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (35.6 g, 179 mmol) in CH2Cl2 (600 mL) was added trimethylsilylisocyanate (82.5 g, 716 mmol, 4 equiv.). The reaction was stirred at rt for 2 h. After concentration, the resulting white solid was dissolved in CH2Cl2 (500 mL) and treated with a solution of HCl (4 M in dioxane, 135 mL, 3 equiv.). The solution quickly became heterogeneous. The suspension was then stirred at rt overnight. Upon concentration, the desired product was isolated as a white solid (33 g, 104%), which was used directly in the next step. [Note: the mass balance was found to be 104%, which arises from additional HCl that could not be removed by standard evaporation under vacuum]. 1H NMR (500 MHz, CD3OD): 4.77 (s, 1H), 4.55 (s, 1H), 3.69 and 3.64 (AB, JAB=12.1, 2H), 3.47 and 3.40 (AB, JAB=11.3, 2H), 2.22 and 2.15 (AB, JAB=11.5, 2H).

Workup

  1. concentrationAfter concentration
  2. dissolutionthe resulting white solid was dissolved in CH2Cl2 (500 mL)
  3. stirringThe suspension was then stirred at rt overnight
  4. concentrationUpon concentration

Sources & evidence

ORD record
ord-7cfe52bab1404b42b6af879cb7f6e5b9
Source dataset
uspto-grants-2011_05
Patent number
US07939527B2

Reaction notes

Loading…