1,4-Dioxane → HCID 53244985, compound

HRID 587323Notes

Reaction equation

HRID 587323 reaction equation
C(N1C=CN=C1)(N1[CH:7]=[CH:6]N=C1)=O.[OH:13]CC1CC1.[Cl:18][C:19]1[CH:20]=[C:21]([C@@H:26]2[C@@H:30]([NH:31][CH3:32])[CH2:29][N:28]([C:33]([CH:35]3[CH2:40][CH2:39][N:38]([C:41]([C:43]4([CH3:46])[CH2:45][CH2:44]4)=[O:42])[CH2:37][CH2:36]3)=[O:34])[CH2:27]2)[CH:22]=[CH:23][C:24]=1[Cl:25].O1[CH2:52][CH2:51][O:50][CH2:49]C1>C(OCC)(=O)C>[CH:52]1([CH2:51][O:50][C:49](=[O:13])[N:31]([C@@H:30]2[C@@H:26]([C:21]3[CH:22]=[CH:23][C:24]([Cl:25])=[C:19]([Cl:18])[CH:20]=3)[CH2:27][N:28]([C:33]([CH:35]3[CH2:40][CH2:39][N:38]([C:41]([C:43]4([CH3:46])[CH2:44][CH2:45]4)=[O:42])[CH2:37][CH2:36]3)=[O:34])[CH2:29]2)[CH3:32])[CH2:7][CH2:6]1

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 682631,1'-CarbonyldiimidazoleHCID 75644CyclopropanemethanolHCID 58009329rac-{4-[(3S,4R)-3-(3,4-Dichloro-phenyl)-4-methylamino-pyrrolidine-1-carbonyl]-piperidin-1-yl}-(1-methyl-cyclopropyl)-methanone

Product 1

HCID 53244985HCID 53244985, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1,1′-carbonyl-diimidazole (102 mg, 0.627 mmol) in dioxane (1 mL) was added hydroxymethylcyclopropane (55 μl, 0.68 mmol). After stirring for 15 min at ambient temperature rac-{4-[(3S,4R)-3-(3,4-dichloro-phenyl)-4-methylamino-pyrrolidine-1-carbonyl]-piperidin-1-yl}-(1-methyl-cyclopropyl)-methanone (50 mg, 0.11 mmol) was added and the solution was irradiated in the microwave for 900 s at 170° C. and 1800 s at 200° C. The reaction mixture was diluted with ethyl acetate (15 mL) and washed with water (15 mL) and brine (15 mL). The organic layers were extracted with ethyl acetate, dried over sodium sulfate and concentrated. Purification by chromatography (SiO2, ethyl acetate:methanol=100:0 to 85:15) afforded the title compound (21 mg, 34%) as a light brown oil. MS m/e: 536.4 [M]+.

Workup

  1. additionwas added
  2. customthe solution was irradiated in the microwave for 900 s at 170° C. and 1800 s at 200° C
  3. washwashed with water (15 mL) and brine (15 mL)
  4. extractionThe organic layers were extracted with ethyl acetate
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customPurification by chromatography (SiO2, ethyl acetate:methanol=100:0 to 85:15)

Sources & evidence

ORD record
ord-8fc85920a85c4893b92ad67ae2aebe19
Source dataset
uspto-grants-2016_01
Patent number
US09226916B2

Reaction notes

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