Dimethylformamide → HCID 66758952, compound

HRID 242605Notes

Reaction equation

HRID 242605 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([OH:35])[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH:16]=[C:17]3[C:23]4[CH:24]=[CH:25][CH:26]=[N:27][C:22]=4[CH2:21][O:20][C:19]4[CH:28]=[CH:29][C:30]([OH:32])=[CH:31][C:18]3=4)[CH2:10][C:9]2([CH3:34])[CH3:33])=[CH:4][CH:3]=1.[H-].[Na+].CN(C)[CH:40]=[O:41]>>[CH2:19]([O:20][C:40](=[O:41])[C:2]([O:32][C:30]1[CH:29]=[CH:28][C:19]2[O:20][CH2:21][C:22]3[N:27]=[CH:26][CH:25]=[CH:24][C:23]=3[C:17](=[CH:16][CH2:15][CH2:14][N:11]3[CH2:12][CH2:13][C:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)([OH:35])[C:9]([CH3:33])([CH3:34])[CH2:10]3)[C:18]=2[CH:31]=1)([CH3:7])[CH3:3])[CH3:18]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 66757704HCID 66757704, compound

Product 1

HCID 66758952HCID 66758952, compoundYield 76%

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) solution of 5-{3-[4-(4-Chloro-phenyl)-4-hydroxy-3,3-dimethyl-piperidin-1-yl]-propylidene}-5,11-dihydro-10-oxa-1-aza-dibenzo[a,d]cyclohepten-7-ol (250 mg, 0.51 mmol) in dimethylformamide (7 mL) was added sodium hydride (60% dispersion in oil, 31 mg, 0.76 mmol). The resulting mixture was stirred at 0° C. for 10 min. Ethyl 2-bromo-2-methyl propionate (149 mg, 0.76 mmol) was added. Stirring at 0° C. was continued 10 min before the mixture was warmed to rt and stirred 4h. The reaction was then partitioned between ethyl acetate and water; the aqueous phase was back-extracted with additional ethyl acetate. The combined organic phases were washed thrice with water, brine and dried over magnesium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (methylene chloride-95:5 methylene chloride:methanol gradient) to afford the titled compound (233 mg, 76%).

Workup

  1. stirringStirring at 0° C.
  2. waitwas continued 10 min before the mixture
  3. temperaturewas warmed to rt
  4. stirringstirred 4h
  5. customThe reaction was then partitioned between ethyl acetate and water
  6. extractionthe aqueous phase was back-extracted with additional ethyl acetate
  7. washThe combined organic phases were washed thrice with water, brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude residue was purified by silica gel chromatography (methylene chloride-95:5 methylene chloride:methanol gradient)

Sources & evidence

ORD record
ord-b6eeeda674dc44528cb20c9d81c0935b
Source dataset
uspto-grants-2014_02
Patent number
US08653096B2

Reaction notes

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