Diisopropylethylamine → (1R,3S,5R)-3-(2-(6-bromoquinoxalin-2-yl)-2-oxoethyl) 2-tert-butyl 2-azabicyclo[3.1.0]hexane-2,3-dicarboxylate

HRID 625610Notes

Reaction equation

HRID 625610 reaction equation
CCN(C(C)C)C(C)C.Br[CH2:11][C:12]([C:14]1[CH:23]=[N:22][C:21]2[C:16](=[CH:17][CH:18]=[C:19]([Br:24])[CH:20]=2)[N:15]=1)=[O:13].[C:25]([O:29][C:30]([N:32]1[C@H:37]([C:38]([OH:40])=[O:39])[CH2:36][C@@H:35]2[C@H:33]1[CH2:34]2)=[O:31])([CH3:28])([CH3:27])[CH3:26]>C(#N)C>[C@@H:33]12[CH2:34][C@@H:35]1[CH2:36][C@@H:37]([C:38]([O:40][CH2:11][C:12]([C:14]1[CH:23]=[N:22][C:21]3[C:16](=[CH:17][CH:18]=[C:19]([Br:24])[CH:20]=3)[N:15]=1)=[O:13])=[O:39])[N:32]2[C:30]([O:29][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:31]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 11020613(1R,3S,5R)-2-(tert-Butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acidHCID 584986562-Bromo-1-(6-bromoquinoxalin-2-yl)ethanone

Product 1

HCID 58498830(1R,3S,5R)-3-(2-(6-bromoquinoxalin-2-yl)-2-oxoethyl) 2-tert-butyl 2-azabicyclo[3.1.0]hexane-2,3-dicarboxylateYield 87%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

DIPEA (0.040 mL, 0.227 mmol) was added to a solution of 2-bromo-1-(6-bromoquinoxalin-2-yl)ethanone (50 mg, 0.152 mmol) and (1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acid (37.9 mg, 0.167 mmol) in acetonitrile (1.5 mL) and the mixture was stirred at rt for 16 h. The solvent was evaporated and the residue was partitioned between EtOAc (20 mL)/aq. sat. NaHCO3 (5 mL). The organic layer was dried (MgSO4), filtered and concentrated to yield crude (1R,3S,5R)-3-(2-(6-bromoquinoxalin-2-yl)-2-oxoethyl) 2-tert-butyl 2-azabicyclo[3.1.0]hexane-2,3-dicarboxylate (63 mg) as orange solid. LC-MS retention time 2.74 min; m/z 476 [M+H]+. (Column PHENOMENEX® Luna 3.0×50 mm 510. Solvent A=90% water: 10% methanol: 0.1% TFA. Solvent B=10% water: 90% methanol: 0.1% TFA. Flow Rate=4 mL/min. Start % B=0. Final % B=100. Gradient Time=3 min. Wavelength=220).

Workup

  1. customThe solvent was evaporated
  2. customthe residue was partitioned between EtOAc (20 mL)/aq
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-284cb59a7bf343bfaef6d9a570f5d489
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

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