Methyl iodide → (2S,5S)-tert-butyl 2-(tert-butyl)-3,5-dimethyl-4-oxoimidazolidine-1-carboxylate

HRID 712813Notes

Reaction equation

HRID 712813 reaction equation
[C:1]([C@H:5]1[N:9]([CH3:10])[C:8](=[O:11])[CH2:7][N:6]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])([CH3:4])([CH3:3])[CH3:2].[Li+].[CH3:20]C([N-]C(C)C)C.C1COCC1.CCCCCCC.IC.[NH4+].[Cl-]>C1COCC1>[C:1]([C@H:5]1[N:9]([CH3:10])[C:8](=[O:11])[C@H:7]([CH3:20])[N:6]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 6328Methyl iodide2×HCID 25517Ammonium ChlorideHCID 688132(S)-tert-Butyl 2-(tert-butyl)-3-methyl-4-oxoimidazolidine-1-carboxylateHCID 2724682Lithium diisopropylamide2×HCID 21263495Tetrahydrofuran heptane

Product 1

HCID 14806604(2S,5S)-tert-butyl 2-(tert-butyl)-3,5-dimethyl-4-oxoimidazolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (S)-tert-butyl 2-(tert-butyl)-3-methyl-4-oxoimidazolidine-1-carboxylate (0.5 g, 1.95 mmol; available from Aldrich#337595) in dry THF (15 ml) cooled to −78° C., LDA 2M in THF/heptane (0.97 ml, 1.95 mmol) was added and the reaction mixture stirred at this temperature for 40 min before adding iodomethane (0.146 ml, 2.34 mmol). The reaction was allowed to warm to RT and stirred for 18 hrs. The reaction mixture was cooled again at −78° C. then LDA 2M in THF/hepatane (0.3 ml) and iodomethane (0.04 ml, 0.6 mmol) were added in sequence. The mixture was allowed to reach RT and further stirred for 5 hrs. The resulting solution was treated with NH4Cl sat sol (5 ml) and extracted with Et2O. The organic phases were collected and washed with NaCl sat sol, dried over Na2SO4 and evaporated in vacuo to afford a residue which was purified by Biotage SNAP-Si column (25 g) eluting with cHex/Et2O 60/40. Collected fractions after solvent evaporation afforded the title compound (D43) (430 mg).

Workup

  1. stirringstirred for 18 hrs
  2. temperatureThe reaction mixture was cooled again at −78° C.
  3. customto reach RT
  4. stirringfurther stirred for 5 hrs
  5. extractionextracted with Et2O
  6. customThe organic phases were collected
  7. washwashed with NaCl
  8. dry with materialdried over Na2SO4
  9. customevaporated in vacuo
  10. customto afford a residue which
  11. customwas purified by Biotage SNAP-Si column (25 g)
  12. washeluting with cHex/Et2O 60/40
  13. customCollected fractions after solvent evaporation

Sources & evidence

ORD record
ord-9c6c5cd6ed314e0aafc1f8c809443b0c
Source dataset
uspto-grants-2015_11
Patent number
US09181279B2

Reaction notes

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