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

HRID 545610Notes

Reaction equation

HRID 545610 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.C(Cl)[Cl:23]>>[ClH:23].[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

4

Reactant 3

HCID 6344DichloromethaneHCID 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

Procedure

To a solution of (S,S)-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (35.6 g, 179 mmol) in CH2Cl2 (600 mL) was added trimethylsilylisocyanate (82.5 g, 716 mmol). After 2 h at rt, the mixture was concentrated, and the resulting white solid was dissolved in CH2Cl2 (500 mL). The solution was then treated with a solution of HCl (4.0 N in 1,4-dioxane, 135 mL). The resulting heterogeneous suspension was then stirred at rt overnight. Upon evaporation of the solvents, the desired product was isolated as a white solid (33 g), which was used directly in the next step. [Note: the mass balance was found to be 104%, which arose 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 (d, J=12.1 Hz, 1H), 3.64 (d, J=12.1 Hz, 1H), 3.47 (d, J=11.3 Hz, 1H), 3.40 (d, J=11.3 Hz, 1H), 2.22 (d, J=11.5 Hz, 1H), 2.15 (d, J=11.5 Hz, 1H).

Workup

  1. concentrationthe mixture was concentrated
  2. dissolutionthe resulting white solid was dissolved in CH2Cl2 (500 mL)
  3. additionThe solution was then treated with a solution of HCl (4.0 N in 1,4-dioxane, 135 mL)
  4. customUpon evaporation of the solvents

Sources & evidence

ORD record
ord-709b184688964bb3b483089acbda3b3a
Source dataset
uspto-grants-2011_05
Patent number
US07935725B2

Reaction notes

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