Methyl iodide → HCID 60009868, compound

HRID 409501Notes

Reaction equation

HRID 409501 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][C@H:9]1[C:21]([OH:23])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24]I>C1COCC1.CC#N>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][C@H:9]1[CH2:21][O:23][CH3:24])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 6328Methyl iodideHCID 11860409Boc-Hyp(Bzl)-OH

Product 1

HCID 60009868HCID 60009868, compoundYield 62.2%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (2S,4R)-4-benzyloxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (15.5 mmol; 5.0 g) in THF (135 mL) is added 1 M THF solution of borane THF complex (31 mmol; 31 mL) at 0° C. under nitrogen. The solution is stirred for 1 hour at room temperature, quenched by dropwise addition of 15 ml of MeOH. After concentrating, the mixture is diluted with dichloromethane and saturated aqueous ammonium chloride solution. The product is extracted twice with dichloromethane. The combined organic layer is washed with brine, dried over MgSO4, filtered, concentrated under reduced pressure to give the crude product. To a solution of crude material in MeCN (20 mL) were added Ag2O (46.5 mmol; 8.9 g) and MeI (155 mmol; 21.8 g) at room temperature, heated and stirred under reflux condition for 3 hours. After filtration and concentration, the resulting mixture is diluted with dichloromethane and saturated aqueous ammonium chloride solution. The product is extracted twice with dichloromethane. The combined organic layer is washed with brine, dried over MgSO4, filtered, concentrated under reduced pressure to give the crude (2S,4R)-4-benzyloxy-2-methoxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (3.1 g).

Workup

  1. customquenched by dropwise addition of 15 ml of MeOH
  2. concentrationAfter concentrating
  3. additionthe mixture is diluted with dichloromethane and saturated aqueous ammonium chloride solution
  4. extractionThe product is extracted twice with dichloromethane
  5. washThe combined organic layer is washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give the crude product
  10. temperatureheated
  11. stirringstirred
  12. temperatureunder reflux condition for 3 hours
  13. filtrationAfter filtration and concentration
  14. additionthe resulting mixture is diluted with dichloromethane and saturated aqueous ammonium chloride solution
  15. extractionThe product is extracted twice with dichloromethane
  16. washThe combined organic layer is washed with brine
  17. dry with materialdried over MgSO4
  18. filtrationfiltered
  19. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f3f0b69a2ed54acb971cdafec5cb4135
Source dataset
uspto-grants-2014_06
Patent number
US08759365B2

Reaction notes

Loading…