Methyl iodide → 1-[(1,1-Dimethylethyl)(dimethyl)silyl]-3,3-dimethyl-2-pyrrolidinone

HRID 1014151Notes

Reaction equation

HRID 1014151 reaction equation
[CH:1](NC(C)C)(C)C.C([Li])CCC.[CH3:13][C:14]([Si:17]([CH3:26])([CH3:25])[N:18]1[CH2:22][CH2:21][CH:20]([CH3:23])[C:19]1=[O:24])([CH3:16])[CH3:15].IC.[NH4+].[Cl-]>C1COCC1>[CH3:13][C:14]([Si:17]([CH3:26])([CH3:25])[N:18]1[CH2:22][CH2:21][C:20]([CH3:1])([CH3:23])[C:19]1=[O:24])([CH3:15])[CH3:16]

Participants

7

Reactant 5

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 578781001-[tert-Butyl(dimethyl)silyl]-3-methylpyrrolidin-2-oneHCID 178418339Butyllithium

Product 1

HCID 578780961-[(1,1-Dimethylethyl)(dimethyl)silyl]-3,3-dimethyl-2-pyrrolidinoneYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

In an oven-dried 1000 ml 3-neck flask fitted with septa and thermometer was charged with diisopropylamine (0.177 mol, 17.9 g) and 300 ml THF. The solution was cooled to 0° C. and n-Butyl lithium (0.193 mol, 77.1 ml of a 2.5M solution in hexanes) was added with stirring over 5 min. After 30 min, the reaction was cooled to −78° C. and a solution of 1-[(1,1-dimethylethyl)(dimethyl)silyl]-3-methyl-2-pyrrolidinone (0.161 mol, 34.3 g) in 80 ml THF was added dropwise keeping reaction temperature below −60° C. Once complete, the reaction was warmed to 20° C. After 1 hr, the reaction was cooled to −78° C. and a solution of Iodomethane (0.177 mol, 25.1 g) in 10 ml of THF was added dropwise over 10 min. The reaction was warmed to 20° C. and stirred for 16 hr, after which time 300 ml saturated NH4Cl was added. The aqueous phase was extracted with ethylacetate (2×150 ml), the organics were combined, dried over MgSO4, filtered and concentrated. The resulting crude oil was purified on 400 g silica (ethyl acetate/hexanes) to yield 29.9 g (82%) of 1-[(1,1-dimethylethyl)(dimethyl)silyl]-3,3-dimethyl-2-pyrrolidinone as a light yellow oil. LCMS (ESI+)=228 m/z (M+). 1H NMR (400 MHz CDCl3) δ 3.31-3.27 (t, 2H, J=6.68 Hz), 1.90-1.87 (t, 2H, J=6.79 Hz), 1.15 (s, 6H), 0.96 (s, 9H), 0.28 (s, 6H).

Workup

  1. customIn an oven-dried 1000 ml 3-neck flask fitted with septa and thermometer
  2. waitAfter 30 min
  3. temperaturethe reaction was cooled to −78° C.
  4. customreaction temperature below −60° C
  5. temperatureOnce complete, the reaction was warmed to 20° C
  6. waitAfter 1 hr
  7. temperaturethe reaction was cooled to −78° C.
  8. temperatureThe reaction was warmed to 20° C.
  9. stirringstirred for 16 hr
  10. extractionThe aqueous phase was extracted with ethylacetate (2×150 ml)
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe resulting crude oil was purified on 400 g silica (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-af5dc3d0ebe748aaa305f00d53a7989d
Source dataset
uspto-grants-2011_07
Patent number
US07982053B2

Reaction notes

Loading…