Acetone → rac-2-{4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl]-3-ethoxy-phenyl}-propan-2-ol

HRID 2263960Notes

Reaction equation

HRID 2263960 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[NH:14][C:15]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=3)([CH3:26])[C:16]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=3)([CH3:18])[N:17]=2)=[C:9]([O:34][CH2:35][CH3:36])[CH:8]=1.[CH3:37][C:38]([CH3:40])=[O:39]>O1CCCC1>[Cl:25][C:22]1[CH:23]=[CH:24][C:19]([C@@:16]2([CH3:18])[C@:15]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=3)([CH3:26])[NH:14][C:13]([C:10]3[CH:11]=[CH:12][C:7]([C:38]([OH:39])([CH3:40])[CH3:37])=[CH:8][C:9]=3[O:34][CH2:35][CH3:36])=[N:17]2)=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 180AcetoneHCID 68683683rac-(4S*,5R*)-2-(4-Bromo-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazoleHCID 178418339Butyllithium

Product 1

HCID 17754634rac-2-{4-[(4S*,5R*)-4,5-Bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazol-2-yl]-3-ethoxy-phenyl}-propan-2-olYield 49%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of n-butyllithium (11.6 mL, 28.95 mmol, 2.5 M solution in hexane, Aldrich) in tetrahydrofuran (50 mL) at −78° C. was added dropwise a solution of rac-(4S*,5R*)-2-(4-bromo-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazole (1.5 g, 2.894 mmol, example 74) in tetrahydrofuran (50 mL). The brown reaction mixture was stirred at −78° C. for 15 min then acetone (2.12 mL, 28.94 mmol) was added dropwise. The color turned yellow at the end of addition. The reaction mixture was stirred at −78° C. for 30 min then quenched with water. The ice bath was removed to let the reaction warmed up to room temperature. The reaction was worked up with water and ethyl acetate. The organic layers were washed with brine and dried over anhydrous sodium sulfate. The solids were filtered off and the filtrate was concentrated to give a yellow residue. Purification of the crude residue by flash chromatography (120 g of silica gel, eluting with 100% ethyl acetate, 2-5% methanol in ethyl acetate) to give the title compound (702 mg, 49%). HR-MS (ES, m/z) calculated for C28H31N2O2Cl2 [(M+H)+] 497.1757, observed 497.1758.

Workup

  1. additionThe color turned yellow at the end of addition
  2. stirringThe reaction mixture was stirred at −78° C. for 30 min
  3. customthen quenched with water
  4. customThe ice bath was removed
  5. temperaturewarmed up to room temperature
  6. washThe organic layers were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationThe solids were filtered off
  9. concentrationthe filtrate was concentrated
  10. customto give a yellow residue
  11. customPurification of the crude residue
  12. washby flash chromatography (120 g of silica gel, eluting with 100% ethyl acetate, 2-5% methanol in ethyl acetate)

Sources & evidence

ORD record
ord-867a236790414cd1b700dbc522022a51
Source dataset
uspto-grants-2010_12
Patent number
US07851626B2

Reaction notes

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