Methyl iodide → HCID 68942647, compound

HRID 332135Notes

Reaction equation

HRID 332135 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]23[CH2:14][CH:13]2[CH2:12][NH:11][CH:10]3[CH3:15])[CH:5]=[CH:6][C:7]=1[Cl:8].[CH3:16]CN(C(C)C)C(C)C.CI>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]23[CH2:14][CH:13]2[CH2:12][N:11]([CH3:16])[CH:10]3[CH3:15])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 81531DiisopropylethylamineHCID 68942614HCID 68942614, compound

Product 1

HCID 68942647HCID 68942647, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a dried, 5 mL round-bottomed flask was added (±)-1-(3,4-dichlorophenyl)-(R/S)-2-methyl-3-aza-bicyclo[3.1.0]hexane, Hunig's Base, and DMF under Ar (g) with stirring. Methyl iodide was added drop wise with stirring over 5 min and the resulting solution stirred under ambient temperature overnight. The solution was concentrated under reduced pressure and purified after drying. The residue was purified by HPLC which failed to remove the impurities. This was further purified on a prep TLC plate eluting with 20/1 CHCl3/MeOH (v/v). The desired band was collected, extracted with CHCl3/MeOH, and concentrated after filtration to afford the desired free base. Yield: 0.005 g 15%; LCMS (+)ESI: m/z=256 [MH]+ (100); 258 [MH+2]+; (65); 1H NMR (300 MHz, CDCl3) δ□: 7.33 (d, H, J=12 Hz, ArH), 7.32 (d, 1H, J=2Hz, ArH), 7.08 (dd, 1H, J=9 Hz, J=2Hz, ArH), 3.31 (q, 1H, J=6Hz, CHNH2), 2.83 (s, 2H, CH2N), 2.32 (s, 3H, NCH3), 1.79 (m, 1H, CH2CH), 1.40 (t(br), 1H, ArCCH2), 0.73 (d, 3H, J=7 Hz, CHCH3), 0.60 (dd, 2H, J=8 Hz, 4Hz, ArCCH2); 13C NMR (75 MHz, CDCl3) δ□: 131.2, 130.1, 128.9, 61.1, 53.8, 36.5, 21.9, 18.4, 11.6.

Workup

  1. stirringwith stirring over 5 min
  2. stirringthe resulting solution stirred under ambient temperature overnight
  3. concentrationThe solution was concentrated under reduced pressure
  4. custompurified
  5. customafter drying
  6. customThe residue was purified by HPLC which
  7. customto remove the impurities
  8. customThis was further purified on a prep TLC plate
  9. washeluting with 20/1 CHCl3/MeOH (v/v)
  10. customThe desired band was collected
  11. extractionextracted with CHCl3/MeOH
  12. concentrationconcentrated
  13. filtrationafter filtration
  14. customto afford the desired free base

Sources & evidence

ORD record
ord-2282b61a697248baaaf7fdc7be81624e
Source dataset
uspto-grants-2014_11
Patent number
US08877798B2

Reaction notes

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