Sodium hydride → HCID 66757650, compound

HRID 242609Notes

Reaction equation

HRID 242609 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+].Br[CH2:39][C:40]([O:42][CH3:43])=[O:41]>CN(C)C=O>[CH3:43][O:42][C:40](=[O:41])[CH2:39][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

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 66757704HCID 66757704, compound

Product 1

HCID 66757650HCID 66757650, compoundYield 48.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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 (0.4 g, 0.814 mmol) was dissolved in dimethyl formamide (10 mL). Sodium hydride (0.029 g, 1.22 mmol, 1.5 equiv, 48 mg of a 60% suspension in mineral oil) was added at room temperature and gas evolution was visible. Methyl bromoacetate (0.187 g, 1.22 mmol, 116 uL) was added and the mixture was stirred at room temperature. After stirring overnight at room temperature, the reaction was quenched with water (10 mL). The resulting suspension was extracted with ethyl acetate (3×10 mL). The combined ethyl acetate extracts were dried over magnesium sulfate, filtered and concentrated in vacuo to give an oil. The crude oil was purified by silica gel chromatography (methylene chloride to 10% methanol in methylene chloride gradient) to afford the title compound as a white solid (222 mg, 48%).

Workup

  1. stirringAfter stirring overnight at room temperature
  2. customthe reaction was quenched with water (10 mL)
  3. extractionThe resulting suspension was extracted with ethyl acetate (3×10 mL)
  4. dry with materialThe combined ethyl acetate extracts were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give an oil
  8. customThe crude oil was purified by silica gel chromatography (methylene chloride to 10% methanol in methylene chloride gradient)

Sources & evidence

ORD record
ord-36e50bb63109471ebacd5a73ba8aaa22
Source dataset
uspto-grants-2014_02
Patent number
US08653096B2

Reaction notes

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