Potassium Carbonate → (1R,3S,5R)-tert-butyl 3-(5-ethynyl-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate

HRID 625618Notes

Reaction equation

HRID 625618 reaction equation
C(=O)([O-])[O-].[K+].[K+].C[Si]([C:11]#[C:12][C:13]1[NH:17][C:16]([C@@H:18]2[CH2:23][C@@H:22]3[C@@H:20]([CH2:21]3)[N:19]2[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[N:15][CH:14]=1)(C)C>CO>[C:12]([C:13]1[NH:17][C:16]([C@@H:18]2[CH2:23][C@@H:22]3[C@@H:20]([CH2:21]3)[N:19]2[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[N:15][CH:14]=1)#[CH:11]

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 58498793(1R,3S,5R)-tert-butyl 3-(5-((trimethylsilyl)ethynyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate

Product 1

HCID 58498700(1R,3S,5R)-tert-butyl 3-(5-ethynyl-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylateYield 97.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

Potassium carbonate (194 mg, 1.40 mmol) was added to a solution of (1R,3S,5R)-tert-butyl 3-(5-((trimethylsilyl)ethynyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (970 mg, 2.81 mmol) in MeOH (30 mL) and the reaction was stirred under nitrogen and then heated at 50° C. (bath temp) for 4 h. The reaction was concentrated to ˜5 mL of volume, diluted with DCM (˜40 mL) and washed with ½ sat brine (˜20 mL). The organics were dried (MgSO4) filtered and concentrated to a tan solid. This material was purified by BIOTAGE® Horizon (40 g SiO2, loaded with DCM, 35-45% EtOAc/hexanes) to yield (1R,3S,5R)-tert-butyl 3-(5-ethynyl-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (747 mg) as a light yellow solid. LC-MS retention time 2.866 min; m/z 272.12 (MH−). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 3u C18 2.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 0.8 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where Solvent A was 5% MeOH/95% H2O/10 mM ammonium acetate and Solvent B was 5% H2O/95% MeOH/10 mM ammonium acetate. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (400 MHz, MeOD) δ ppm 7.18 (br. s., 1H), 4.59 (br. s., 1H), 3.36-3.64 (m, 2H), 2.46 (dd, J=13.2, 8.9 Hz, 1H), 2.18-2.31 (m, 1H), 1.64-1.74 (m, 1H), 1.18-1.45 (m, 9H), 0.83 (dt, J=8.5, 5.8 Hz, 1H), 0.56 (br. s., 1H).

Workup

  1. concentrationThe reaction was concentrated to ˜5 mL of volume
  2. additiondiluted with DCM (˜40 mL)
  3. washwashed with ½
  4. dry with materialThe organics were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated to a tan solid
  7. customThis material was purified by BIOTAGE® Horizon (40 g SiO2, loaded with DCM, 35-45% EtOAc/hexanes)

Sources & evidence

ORD record
ord-be0bdd0a05f44646a294fac9828fb3bd
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

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