Acetic Acid → HCID 19884960, compound

HRID 846197Notes

Reaction equation

HRID 846197 reaction equation
[C:1]1([CH:7](N)[CH2:8][CH2:9][O:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]([CH3:21])=[CH:13][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:23](#N)C.[CH2:26]=[O:27].[C:28]([BH3-])#[N:29].[Na+].[C:32]([OH:35])(=[O:34])C>>[C:32]([OH:35])(=[O:34])[C:26]([OH:10])=[O:27].[CH3:23][N:29]([CH3:28])[CH:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH2:8][CH2:9][O:10][C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([CH3:21])=[CH:13][CH:12]=1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 712FormaldehydeHCID 6342AcetonitrileHCID 5003444Sodium cyanoborohydrideHCID 19884969HCID 19884969, compound

Product 1

HCID 19884960HCID 19884960, compound

Procedure

A 250 ml three-neck round bottom flask was charged with 2.2 g (7.6 mmol) of 1-phenyl-3-(4-methyl-1-naphthalenyloxy)propanamine and 100 ml of acetonitrile. To the mixture was added a 37% formaldehyde solution (3.02 ml, 37.8 mmol). The mixture was stirred for approximately 20 minutes while moderate heat was applied to maintain the reaction mixture as a solution. Next, 760 mg (12.1 mmol) of sodium cyanoborohydride was added to the reaction mixture, and the mixture was stirred for five hours at room temperature. The pH of the reaction mixture was maintained at approximately 6.5 by the addition of glacial acetic acid. The reaction mixture was acidified and stirred for 30 minutes. The mixture was concentrated under vacuum and made basic by the addition of 5N sodium hydroxide. Ten drops of triethylamine were added. The mixture was extracted three times with diethyl ether, and the organic extracts were combined and washed with water and a saturated sodium chloride solution, and dried over anhydrous sodium sulfate. The organic phase was concentrated under vacuum to provide 2.6 g of an oil. The oil was purified by high pressure liquid chromatography employing a methanol/methylene chloride gradient as the eluent. The free base was converted to the oxalate salt and recrystallized from ethyl acetate to provide 1.5 g of the title compound. mp=110°-112.5° C.

Workup

  1. temperaturewhile moderate heat
  2. temperatureto maintain the reaction mixture as a solution
  3. stirringthe mixture was stirred for five hours at room temperature
  4. stirringstirred for 30 minutes
  5. concentrationThe mixture was concentrated under vacuum
  6. additionmade basic by the addition of 5N sodium hydroxide
  7. additionTen drops of triethylamine were added
  8. extractionThe mixture was extracted three times with diethyl ether
  9. washwashed with water
  10. dry with materiala saturated sodium chloride solution, and dried over anhydrous sodium sulfate
  11. concentrationThe organic phase was concentrated under vacuum

Sources & evidence

ORD record
ord-f35c6bca39d340d99f3e5d6637dfb513
Source dataset
uspto-grants-1992_08
Patent number
US05135947

Reaction notes

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