Ammonium Chloride → (2S,5R)-tert-butyl 2-(tert-butyl)-5-(4-chlorobutyl)-3,5-dimethyl-4-oxoimidazolidine-1-carboxylate

HRID 712814Notes

Reaction equation

HRID 712814 reaction equation
[C:1]([C@H:5]1[N:9]([CH3:10])[C:8](=[O:11])[C@H:7]([CH3:12])[N:6]1[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])([CH3:4])([CH3:3])[CH3:2].[Li+].CC([N-]C(C)C)C.C1COCC1.CCCCCCC.Br[CH2:41][CH2:42][CH2:43][CH2:44][Cl:45].[NH4+].[Cl-]>C1COCC1>[C:1]([C@H:5]1[N:9]([CH3:10])[C:8](=[O:11])[C@:7]([CH2:41][CH2:42][CH2:43][CH2:44][Cl:45])([CH3:12])[N:6]1[C:13]([O:15][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:14])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 813641-Bromo-4-chlorobutaneHCID 2724682Lithium diisopropylamideHCID 14806604(2S,5S)-tert-butyl 2-(tert-butyl)-3,5-dimethyl-4-oxoimidazolidine-1-carboxylateHCID 21263495Tetrahydrofuran heptane

Product 1

HCID 117966772(2S,5R)-tert-butyl 2-(tert-butyl)-5-(4-chlorobutyl)-3,5-dimethyl-4-oxoimidazolidine-1-carboxylateYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (2S,5S)-tert-butyl 2-(tert-butyl)-3,5-dimethyl-4-oxoimidazolidine-1-carboxylate (D43) (430 mg, 1.59 mmol) in dry THF (15 ml) cooled to −78° C., LDA 2M in THF/heptane (1.2 ml, 2.38 mmol) was added and the reaction mixture stirred at this temperature for 40 min before adding 1-bromo-4-chloro-butane (0.27 ml, 2.38 mmol). The reaction was allowed to warm to RT and left stirring for 3 hrs. The resulting solution was treated with NH4Cl sat sol (5 ml) and extracted with Et2O (3×10 ml). 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 (D44) (465 mg).

Workup

  1. waitleft
  2. stirringstirring for 3 hrs
  3. extractionextracted with Et2O (3×10 ml)
  4. customThe organic phases were collected
  5. washwashed with NaCl
  6. dry with materialdried over Na2SO4
  7. customevaporated in vacuo
  8. customto afford a residue which
  9. customwas purified by Biotage SNAP-Si column (25 g)
  10. washeluting with cHex/Et2O 60/40
  11. customCollected fractions after solvent evaporation

Sources & evidence

ORD record
ord-9c8e1f109c4c4d2d9f01d05b31cf4d68
Source dataset
uspto-grants-2015_11
Patent number
US09181279B2

Reaction notes

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