Diiodomethane → 2-(1,1-Dimethylethyl) 5-(9H-fluoren-9-ylmethyl) 2,5-diazabicyclo[4.1.0]heptane-2,5-dicarboxylate

HRID 2173431Notes

Reaction equation

HRID 2173431 reaction equation
[N:1]1([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH:6]=[CH:5][N:4]([C:7]([O:9][CH2:10][CH:11]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:17]3[C:12]2=[CH:13][CH:14]=[CH:15][CH:16]=3)=[O:8])[CH2:3][CH2:2]1.[CH2:31]([Zn]CC)C.ICI>CCOCC>[CH:6]12[CH2:31][CH:5]1[N:4]([C:7]([O:9][CH2:10][CH:11]1[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=3[C:18]3[C:23]1=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:8])[CH2:3][CH2:2][N:1]2[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25]

Participants

5

Reactant 3

HCID 6346DiiodomethaneHCID 67518168HCID 67518168, compoundHCID 178418750HCID 178418750, compound

Product 1

HCID 1015019572-(1,1-Dimethylethyl) 5-(9H-fluoren-9-ylmethyl) 2,5-diazabicyclo[4.1.0]heptane-2,5-dicarboxylate

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

In a pre-dried round bottom flask, tert-butyl 9H-fluoren-9-ylmethyl 2,3-dihydropyrazine-1,4-dicarboxylate (1.5 g, 3.69 mmol) was dissolved in anhydrous ether (80 ml) under N2. Diethylzinc (27.4 ml, 27.4 mmol) in ether (1M) was added in via syringe. Diiodomethane (1.904 ml, 23.60 mmol) was added. Let reaction stir at room temperature overnight. On next day, reaction was quenched by adding 5 mL of saturated aqueous NH4Cl. Reaction mixture was filtered over a pad of Celite® and filtering cake was washed with ether (25 mL×2). Then layers were separated and aqueous portion was extracted with ether (50 mL). The combined organic phases were washed with water (50 mL) and brine (50 mL), dried over anhydrous Na2SO4. Concentration at reduced pressure afforded crude product that was purified by silica gel column chromatography (40 gram silica gel column, eluted with 0-100% EtOAc/Hexane gradient). Removing solvent gave the title compound. 1H NMR (ppm) (500 MHz, CDCl3): δ 7.76 (2H, d, J=7.59 Hz), 7.66-7.53 (2H, m), 7.40 (2H, t, J=7.50 Hz), 7.31 (2H, t, J=7.45 Hz), 4.52-4.44 (2H, m), 4.26 (1H, t, J=7.13 Hz), 3.62-2.90 (6H, m), 1.50 (9H, s), 1.25-0.89 (1H, m). 0.55-0.39 (1H, m); LC/MS (M+23)+=443.13;

Workup

  1. customreaction
  2. waitOn next day
  3. customreaction
  4. customwas quenched
  5. additionby adding 5 mL of saturated aqueous NH4Cl
  6. customReaction mixture
  7. filtrationwas filtered over a pad of Celite®
  8. filtrationfiltering cake
  9. washwas washed with ether (25 mL×2)
  10. customThen layers were separated
  11. extractionaqueous portion was extracted with ether (50 mL)
  12. washThe combined organic phases were washed with water (50 mL) and brine (50 mL)
  13. dry with materialdried over anhydrous Na2SO4
  14. concentrationConcentration at reduced pressure
  15. customafforded crude product that
  16. customwas purified by silica gel column chromatography (40 gram silica gel column, eluted with 0-100% EtOAc/Hexane gradient)

Sources & evidence

ORD record
ord-78f9e28565124cbcbb575af77527be1a
Source dataset
uspto-grants-2015_06
Patent number
US09056859B2

Reaction notes

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