Methyl iodide → Tert-butyl 3-methoxy-4-methylenepyrrolidine-1-carboxylate

HRID 2040914Notes

Reaction equation

HRID 2040914 reaction equation
[OH:1][CH:2]1[C:6](=[CH2:7])[CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[H-].[Na+].[CH3:17]I>C1COCC1>[CH3:17][O:1][CH:2]1[C:6](=[CH2:7])[CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 11446960Tert-butyl 3-hydroxy-4-methylidenepyrrolidine-1-carboxylate

Product 1

HCID 57493865Tert-butyl 3-methoxy-4-methylenepyrrolidine-1-carboxylateYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of tert-butyl 3-hydroxy-4-methylenepyrrolidine-1-carboxylate (0.257 g, 1.29 mmol; prepared as described by Alcaraz, Lilian; Cridland, Andrew; Kinchin, Elizabeth Organic Letters, 2001, vol. 3, #25 p. 4051-4054) in 8 mL of THF, stirred at r.t. under a nitrogen atmosphere was added NaH. After 0.5 h stirring at r.t., methyl iodide (0.057 g, 1.42 mmol) was added and the resulting mixture stirred at r.t. for 2 h. After overnight resting, the reaction was quenched with water, extracted with EtOAc which was washed with brine, dried over Na2SO4 and evaporated to dryness affording a crude, purified by means of automated flash chromatography (SP01®TM-Biotage; gradient Petroleum Ether-EtOAc from 9:1 to 7:3) giving 165 mg of the title compound. Yield: 60%.

Workup

  1. stirringthe resulting mixture stirred at r.t. for 2 h
  2. waitAfter overnight resting
  3. customthe reaction was quenched with water
  4. extractionextracted with EtOAc which
  5. washwas washed with brine
  6. dry with materialdried over Na2SO4
  7. customevaporated to dryness
  8. customaffording a crude
  9. custompurified by means of automated flash chromatography (SP01®TM-Biotage; gradient Petroleum Ether-EtOAc from 9:1 to 7:3)

Sources & evidence

ORD record
ord-9462a9710bf442889f93444c3126d25b
Source dataset
uspto-grants-2013_11
Patent number
US08580962B2

Reaction notes

Loading…