Water → HCID 70299656, compound

HRID 1378419Notes

Reaction equation

HRID 1378419 reaction equation
[CH:1]1[C:6]2[NH:7][C:8]3[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=3[CH2:10][CH2:11][CH2:12][C:5]=2[CH:4]=[CH:3][CH:2]=1.C([CH:19]([C:23](Cl)=[O:24])[C:20](Cl)=[O:21])C.[OH-:26].[Na+].O.[C:29]1([CH3:35])C=CC=CC=1>>[CH2:29]([O:26][C:23](=[O:24])[CH2:19][C:20]([N:7]1[C:6]2[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=2[CH2:12][CH2:11][CH2:10][C:9]2[CH:13]=[CH:14][CH:15]=[CH:16][C:8]1=2)=[O:21])[CH3:35]

Participants

6

Reactant 5

HCID 962WaterHCID 1140Toluene2×HCID 14798Sodium HydroxideHCID 109209242-Ethylpropanedioyl dichlorideHCID 12412218HCID 12412218, compound

Product 1

HCID 70299656HCID 70299656, compoundYield 95%

Procedure

In a 100 ml roundbottom flask equipped with magnetical stirring, thermometer and addition funnel, 5,6,7,12-tetrahydrodibenzo[b,g]azocine (2.1 g, 0.01 mol, prepared in a similar way as described in Chem. Pharm. Bull., 26, (1978), 942) was dissolved in dry toluene (60 ml) and ethyl malonyl chloride (2.0 g, 0.013 mol) was slowly added. The reaction mixture was heated at reflux temperature for 2 h and then allowed to cool to room temperature. Under stirring, 0.2N NaOH (5 ml) and water (60 ml) were added. More toluene was added (100 ml) and the phases were separated. The organic phase was washed with water (3×75 ml) and brine (75 ml). After drying (MgSO4), the organic phase was evaporated in vacuo affording 3.1 g (95% of 3-(6,7-dihydro-5H-dibenzo[b,g]azocin-12-yl)-3-oxopropionic acid ethyl ester as an oil. LiAlH4 (1.4 g, 0.037 mol) was placed in a dry, 250 ml, three-necked, round-bottom flask, equipped with thermometer, magnetical stirring and addition funnel. Under nitrogen, dry toluene (60 ml) was added followed by slow addition of THF (6 ml). A temperature at 15°-25° C. was assured by the use of a water/ice-bath. After stirring for 30 minutes, the above amide (3.0 g, 0.0093 mol) was dissolved in dry toluene (18 ml) and slowly added to the LiAlH4 -slurry at 20°-25° C. The reaction mixture was left stirring overnight at room temperature. Water (1.5 ml) was slowly added dropwise, followed by 4N NaOH (1.5 ml) and finally water (4.5 ml). The resulting precipitate was filtered off on filter aid (celite). The toluene solution was dried (MgSO4) and evaporated in vacuo. The crude residue was purified by column chromatography on silica gel (75 g), using a mixture of heptane and ethyl acetate (1:1) as eluent. This afforded 0.4 g (48%) of 3-(6,7-dihydro-5H-dibenzo-[b,g]azocin-12-yl)-1-propanol, as an oil. Rf : 0.37 (SiO2 ; n-heptane/ethyl acetate=1:1).

Workup

  1. customIn a 100 ml roundbottom flask equipped with magnetical stirring
  2. additionthermometer and addition funnel
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux temperature for 2 h
  5. customthe phases were separated
  6. washThe organic phase was washed with water (3×75 ml) and brine (75 ml)
  7. dry with materialAfter drying (MgSO4)
  8. customthe organic phase was evaporated in vacuo

Sources & evidence

ORD record
ord-9a108355107945da837d3a28c14f83ea
Source dataset
uspto-grants-1997_09
Patent number
US05668129

Reaction notes

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