2,6-Lutidine → (4S,5R)-1-[[4-[[4-(3,4-Dichlorophenoxy)-1-piperidinyl]methyl]-1-piperidinyl]acetyl]-3,4-dimethyl-5-phenyl-2-imidazolidinone

HRID 1727846Notes

Reaction equation

HRID 1727846 reaction equation
N1C(C)=CC=CC=1C.[CH3:9][N:10]1[C@@H:14]([CH3:15])[C@@H:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[NH:12][C:11]1=[O:22].Br[CH2:24][C:25](Br)=[O:26].C(=O)(O)[O-].[Na+].[Cl:33][C:34]1[CH:35]=[C:36]([CH:51]=[CH:52][C:53]=1[Cl:54])[O:37][CH:38]1[CH2:43][CH2:42][N:41]([CH2:44][CH:45]2[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]2)[CH2:40][CH2:39]1>O1CCCC1.O>[Cl:33][C:34]1[CH:35]=[C:36]([CH:51]=[CH:52][C:53]=1[Cl:54])[O:37][CH:38]1[CH2:39][CH2:40][N:41]([CH2:44][CH:45]2[CH2:46][CH2:47][N:48]([CH2:24][C:25]([N:12]3[C@H:13]([C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=4)[C@H:14]([CH3:15])[N:10]([CH3:9])[C:11]3=[O:22])=[O:26])[CH2:49][CH2:50]2)[CH2:42][CH2:43]1

Participants

8

Reactant 5

HCID 79372,6-LutidineHCID 61147Bromoacetyl bromideHCID 516892Sodium BicarbonateHCID 6931391(4R,5S)-(-)-1,5-Dimethyl-4-phenyl-2-imidazolidinoneHCID 689343214-(3,4-Dichlorophenoxy)-1-(4-piperidinylmethyl)-piperidine

Product 1

HCID 68932010(4S,5R)-1-[[4-[[4-(3,4-Dichlorophenoxy)-1-piperidinyl]methyl]-1-piperidinyl]acetyl]-3,4-dimethyl-5-phenyl-2-imidazolidinone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

2,6Lutidine (18.26 mL) was added to a stirred suspension of (4R,5S)-1,5-dimethyl-4-phenylimidazolidin-2-one (27.33 g) in anhydrous tetrahydrofuran (300 mL) at 0° C. under nitrogen. Bromoacetyl bromide (11.95 mL) was added over 5 minutes and the mixture was stirred for a further 15 minutes. Saturated aqueous sodium bicarbonate solution (300 mL) was added followed by 4-(3,4-dichlorophenoxy)-1-(4-piperidinylmethyl)piperidine (44.86 g) and the mixture was stirred for 24 hours at ambient temperature. Water (300 mL) was added and the mixture was extracted with tert-butyl methyl ether (300 mL). The organic extracts were dried over anhydrous magnesium sulfate, filtered and evaporated under reduced pressure. The residue was suspended in tert-butyl methyl ether (300 mL) and stirred for 3 days. The resulting solid was filtered, washed with tert-butyl methyl ether (3×50 mL) and dried in under reduced pressure to give the title compound (45.65 g) as a solid.

Workup

  1. stirringthe mixture was stirred for 24 hours at ambient temperature
  2. extractionthe mixture was extracted with tert-butyl methyl ether (300 mL)
  3. dry with materialThe organic extracts were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. stirringstirred for 3 days
  7. filtrationThe resulting solid was filtered
  8. washwashed with tert-butyl methyl ether (3×50 mL)
  9. customdried in under reduced pressure

Sources & evidence

ORD record
ord-4511fc166f374c73934748b673e2b6b9
Source dataset
uspto-grants-2009_02
Patent number
US07495013B2

Reaction notes

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