Sodium Bicarbonate → N-[3-(Quinolin-7-yloxy)propyl]-2,3-dihydro-7-hydroxy-1,4-benzodioxin-2-methanamine

HRID 2254305Notes

Reaction equation

HRID 2254305 reaction equation
O.Cl.Cl.[N:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:14][CH2:15][CH2:16][CH2:17][NH:18][CH2:19][CH:20]3[O:25][C:24]4[CH:26]=[C:27]([O:30]C)[CH:28]=[CH:29][C:23]=4[O:22][CH2:21]3)[CH:12]=2)[CH:7]=[CH:6][CH:5]=1.C(=O)(O)[O-].[Na+]>Br>[N:4]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:14][CH2:15][CH2:16][CH2:17][NH:18][CH2:19][CH:20]3[O:25][C:24]4[CH:26]=[C:27]([OH:30])[CH:28]=[CH:29][C:23]=4[O:22][CH2:21]3)[CH:12]=2)[CH:7]=[CH:6][CH:5]=1

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 19745015N-[3-(Quinolin-7-yloxy)propyl]-2,3-dihydro-7-methoxy-1,4-benzodioxin-2-methanamine dihydrochloride monohydrate

Product 1

HCID 9969148N-[3-(Quinolin-7-yloxy)propyl]-2,3-dihydro-7-hydroxy-1,4-benzodioxin-2-methanamineYield 68.2%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Procedure

N-[3-(Quinolin-7-yloxy)propyl]-2,3-dihydro-7-methoxy-1,4-benzodioxin-2-methanamine dihydrochloride monohydrate (0.94 g, 2.0 mmole), prepared above in Example 4, was dissolved in 10 ml of 48% HBr and refluxed for 24 hours under a nitrogen atmosphere. Upon cooling, the mixture was poured into 100 ml of saturated sodium bicarbonate solution to which 50 g of ice had been added. When the ice had melted, the mixture was extracted three times with 150 ml portions of 3:1 dichloromethane-isopropanol, the extracts dried over sodium sulfate, filtered, and concentrated in vacuum. The residue was column chromatographed on 50 g of silica gel with 3% methanol/chloroform and the product-containing fractions were combined and concentrated in vacuum. The crude free base thus obtained was crystallized from 50 ml of ethanol with the addition of 3 ml of 4N isopropanolic HCl to give 0.5 g of the title compound as a yellow dihydrochloride monohydrate, m.p. 245°-246° C.

Workup

  1. temperaturerefluxed for 24 hours under a nitrogen atmosphere
  2. temperatureUpon cooling
  3. additionhad been added
  4. extractionthe mixture was extracted three times with 150 ml portions of 3:1 dichloromethane-isopropanol
  5. dry with materialthe extracts dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuum
  8. customchromatographed on 50 g of silica gel with 3% methanol/chloroform
  9. concentrationconcentrated in vacuum
  10. customThe crude free base thus obtained
  11. customwas crystallized from 50 ml of ethanol with the addition of 3 ml of 4N isopropanolic HCl

Sources & evidence

ORD record
ord-338c58532f6b4f689f48056d151428fa
Source dataset
uspto-grants-1993_08
Patent number
US05235055

Reaction notes

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