Methyl iodide → (1S,5R)-5-Methyl-4,6-dioxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octan-1-ylcarboxylic acid tert-butyl ester

HRID 1917355Notes

Reaction equation

HRID 1917355 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([C@@:10]12[CH2:17][CH2:16][C:15](=[O:18])[C@@H:14]1[C:13](=[O:19])[N:12]([C@@H:20]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH3:21])[CH2:11]2)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH3:28]I>CN(C)C=O>[C:3]([O:7][C:8]([C@@:10]12[CH2:17][CH2:16][C:15](=[O:18])[C@:14]1([CH3:28])[C:13](=[O:19])[N:12]([C@@H:20]([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[CH3:21])[CH2:11]2)=[O:9])([CH3:4])([CH3:5])[CH3:6]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67490920(1S,5R)-4,6-dioxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octan-1-ylcarboxylic acid tert-butyl ester

Product 1

HCID 67490869(1S,5R)-5-Methyl-4,6-dioxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octan-1-ylcarboxylic acid tert-butyl esterYield 75.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

N,N-Dimethylformamide (2.0 mL) was added to sodium hydride (152 mg, 3.48 mmol) in an argon atmosphere. A solution of (1S,5R)-4,6-dioxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octan-1-ylcarboxylic acid tert-butyl ester (1.00 g, 2.91 mmol) in N,N-dimethylformamide (8.0 mL) was added dropwise to this suspension under ice-cooling, and the mixture was stirred at 0° C. for 30 minutes. Subsequently, methyl iodide (0.217 mL, 3.49 mmol) was added dropwise under ice-cooling, and the mixture was stirred at room temperature for 2.5 hours. The reaction solution was ice-cooled and then the reaction was quenched with water, followed by extraction with ethyl acetate. Then, the organic layer was washed with water and brine, dried over anhydrous sodium sulfate, and filtered. Thereafter, the solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography (hexane:ethyl acetate=2:1→1:1) to give 0.79 g of the title compound as a pale yellow solid.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringthe mixture was stirred at room temperature for 2.5 hours
  4. temperaturecooled
  5. customthe reaction was quenched with water
  6. extractionfollowed by extraction with ethyl acetate
  7. washThen, the organic layer was washed with water and brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. customThereafter, the solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-24bacb724d9e4f3390b7261b15f1e8d4
Source dataset
uspto-grants-2013_12
Patent number
US08618094B2

Reaction notes

Loading…