Methyl iodide → (S)-di-tert-butyl 4,4-dimethyl-5-oxopyrrolidine-1,2-dicarboxylate

HRID 734196Notes

Reaction equation

HRID 734196 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12](=[O:13])[CH:11]([CH3:14])[CH2:10][C@H:9]1[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:22][Si](C)(C)[N-][Si](C)(C)C.[Li+].CI>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[C:12](=[O:13])[C:11]([CH3:22])([CH3:14])[CH2:10][C@H:9]1[C:15]([O:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[O:16])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 21015973tert-Butyl N-tert-butoxycarbonyl-4-methyl-L-pyroglutamate

Product 1

HCID 15381580(S)-di-tert-butyl 4,4-dimethyl-5-oxopyrrolidine-1,2-dicarboxylateYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of tert-butyl N-tert-butoxycarbonyl-4-methyl-L-pyroglutamate (1.2 g, 4.0 mmol) in tetrahydrofuran (20 mL) stirring at −78° C., was added a 1 M solution of lithium hexamethyldisilazide in tetrahydrofuran (4.4 mL, 4.4 mmol) dropwise over 5 minutes. After 30 minutes, methyliodide (0.33 mL, 5.2 mmol) was added. After an additional 3 hours at −78° C., the cooling bath was removed and 50% saturated aqueous ammonium chloride (40 mL) was added. The solution was stirred for 20 minutes, then extracted with ether (2×50 mL). The combined organic layers were washed with water (2×25 mL), saturated sodium bicarbonate (2×25 mL), brine (50 mL), dried (Na2SO4), filtered and concentrated to give Boc-PyroGlu(4,4-dimethyl)-OtBu (0.673 g, 54%).

Workup

  1. waitAfter an additional 3 hours at −78° C.
  2. customthe cooling bath was removed
  3. addition50% saturated aqueous ammonium chloride (40 mL) was added
  4. extractionextracted with ether (2×50 mL)
  5. washThe combined organic layers were washed with water (2×25 mL), saturated sodium bicarbonate (2×25 mL), brine (50 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-51625dde30eb4fd1a3ca51c3ce8fe188
Source dataset
uspto-grants-2009_09
Patent number
US07592316B2

Reaction notes

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