Potassium Carbonate → HCID 67492637, compound

HRID 1945557Notes

Reaction equation

HRID 1945557 reaction equation
[CH2:1]([O:3][C:4](=[O:9])[C:5](Br)([CH3:7])[CH3:6])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[C:16]([O:20][C:21]([N:23]1[CH2:28][C@@H:27]2[CH2:29][C@H:24]1[CH2:25][NH:26]2)=[O:22])([CH3:19])([CH3:18])[CH3:17]>C(#N)C>[C:16]([O:20][C:21]([N:23]1[CH2:28][C@@H:27]2[CH2:29][C@H:24]1[CH2:25][N:26]2[C:5]([C:4]([O:3][CH2:1][CH3:2])=[O:9])([CH3:7])[CH3:6])=[O:22])([CH3:19])([CH3:17])[CH3:18]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptane

Product 1

HCID 67492637HCID 67492637, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

2-Bromo-2-methylpropionic acid ethyl ester (155 μL, 1.06 mmol) was added to a solution of potassium carbonate (145 mg, 1.05 mmol) and (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (200 mg, 1.01 mmol) in anhydrous acetonitrile (1 mL). The resulting mixture was heated at 80° C. for 48 h, then cooled to ambient temperature and partitioned between EtOAc and water. The organic layer was separated, washed with brine, then dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH; 100:0 to 98:2) to give (1S,4S)-5-(1-ethoxycarbonyl-1-methylethyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester as a pale brown oil. To a solution of (1S,4S)-5-(1-ethoxycarbonyl-1-methylethyl)-2,5-diazabicyclo[2.2.1]-heptane-2-carboxylic acid tert-butyl ester (1 mmol) in anhydrous THF (5 mL) at 0° C., a solution of LiAlH4 (1 M in THF, 3.2 mL, 3.2 mmol) was added dropwise. The reaction mixture was allowed to warm to ambient temperature and stirred for 1 h. The reaction mixture was loaded onto an Isolute® SCX-2 cartridge (10 g), washed with MeOH before the desired product was eluted using 2 M NH3 in MeOH. The product was collected and concentrated in vacuo to afford the title compound as a brown oil (168 mg, 99%). 1H NMR (CDCl3, 400 MHz) δ 3.37 (bs, 1 H); 3.31 (d, J=10.2 Hz, 1 H); 3.21 (d, J=10.2 Hz, 1 H); 3.15-3.00 (m, 2 H); 2.81-2.61 (m, 2 H); 2.45 (s, 2 H); 1.76 (d, J=10.0 Hz, 1 H); 1.56 (d, J=10.0 Hz, 1 H); 1.46 (t, J=5.02 Hz, 1 H); 1.03 (s, 3 H) and 1.00 (s, 2 H).

Workup

  1. temperaturecooled to ambient temperature
  2. custompartitioned between EtOAc and water
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH; 100:0 to 98:2)

Sources & evidence

ORD record
ord-88014e0c958643759dc474ccf1f8bf50
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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