1-Methylimidazole → HCID 69819243, compound

HRID 1006359Notes

Reaction equation

HRID 1006359 reaction equation
[ClH:1].Cl.[CH:3]([C@H:16]1[N:21]2[CH2:22][CH2:23][CH2:24][C@H:20]2[CH2:19][N:18]([CH2:25][C:26]2[CH:31]=[C:30](Br)[CH:29]=[CH:28][C:27]=2[O:33][CH3:34])[CH2:17]1)([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:41][N:42]1[CH:46]=[CH:45][N:44]=[CH:43]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])O.[Na+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[ClH:1].[ClH:1].[CH:3]([C@H:16]1[N:21]2[CH2:22][CH2:23][CH2:24][C@H:20]2[CH2:19][N:18]([CH2:25][C:26]2[CH:31]=[C:30]([C:46]3[N:42]([CH3:41])[CH:43]=[N:44][CH:45]=3)[CH:29]=[CH:28][C:27]=2[O:33][CH3:34])[CH2:17]1)([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

8

Reactant 5

HCID 13901-MethylimidazoleHCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 516892Sodium BicarbonateHCID 69819834HCID 69819834, compound

Product 1

HCID 69819243HCID 69819243, compoundYield 308.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

(4R,8aS)-4-Benzhydryl-2-(2-methoxy-5-bromobenzyl)octahydropyrrolo[1,2-a]pyrazine dihydrochloride (29.8 mg) was dissolved in N,N-dimethylformamide (2.0 ml). Then potassium carbonate (85.6 mg), N-methylimidazol (43.6 mg), palladium acetate (3.98 mg) and triphenylphosphine (9.29 mg) were added to the solution at room temperature. The whole was stirred for 10 hours at 140° C. The reaction mixture was poured into aqueous sodium hydrogen carbonate. The whole mixture was extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The resulting residue was purified by preparative TLC (0.5 mm) with a mixture of dichloromethane and methanol (10:1) as an eluent, and treated with 4N hydrogen chloride in ethyl acetate to give (4R,8aS)-4-benzhydryl-2-[2-methoxy-5-(3-methyl-3H-imidazol-4-yl)benzyl]octahydropyrrolo[1,2-a]pyrazine dihydrochloride (46.1 mg) as a colorless powder.

Workup

  1. extractionThe whole mixture was extracted with ethyl acetate
  2. washThe extract was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customevaporated under reduced pressure
  5. customThe resulting residue was purified by preparative TLC (0.5 mm) with a mixture of dichloromethane and methanol (10:1) as an eluent
  6. additiontreated with 4N hydrogen chloride in ethyl acetate

Sources & evidence

ORD record
ord-ae577e91d1a54076ad10191efa2df8d5
Source dataset
uspto-grants-2004_09
Patent number
US06787543B2

Reaction notes

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