Ethyl Acetate → 4-Benzyl-2-({2-[(thiophen-2-yl)methyl]phenoxy}methyl)morpholine

HRID 1415401Notes

Reaction equation

HRID 1415401 reaction equation
[CH2:1]([N:8]1[C:13](=O)[CH2:12][O:11][CH:10]([CH2:15][O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH2:23][C:24]2[S:28][CH:27]=[CH:26][CH:25]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C(OCC)(=O)C.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1C=CC=CC=1.CCOCC.O>[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([CH2:15][O:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH2:23][C:24]2[S:28][CH:27]=[CH:26][CH:25]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 9357Potassium Sodium TartrateHCID 13682470HCID 13682470, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 136824814-Benzyl-2-({2-[(thiophen-2-yl)methyl]phenoxy}methyl)morpholineYield 90.2%

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

A solution of 23 g of 4-benzyl-2-[2-(2-thenyl)phenoxymethyl]-morpholin-5-one in 200 ml of benzene was added dropwise to a suspension of 7 g of lithium aluminum hydride in 200 ml of ether with stirring and cooling. The resulting mixture was heated under reflux with stirring for 5 hours. To the mixture was added 10 ml of ethyl acetate, and the whole mixture was stirred for 30 minutes. To the mixture were added water under cooling and then 300 ml of a saturated aqueous Rochelle salt solution, and the resulting mixture was stirred for 30 minutes. The organic layer was collected and dried over anhydrous magnesium sulfate. The solvent was distilled off to give 20 g of 4-benzyl-2-[2-(2-thenyl)phenoxymethyl]morpholine as an oil. The oil was dissolved in ether, and a mixture of 4.8 g of oxalic acid in ether and ethanol was added to the solution to give 23 g of the corresponding oxalate salt as colorless crystals, melting at 179°-181.5° C. The thus-obtained oxalate was converted into the free base, which was used as the starting compound of Example 1.

Workup

  1. temperaturecooling
  2. temperatureThe resulting mixture was heated
  3. temperatureunder reflux
  4. stirringwith stirring for 5 hours
  5. stirringthe whole mixture was stirred for 30 minutes
  6. temperatureunder cooling
  7. customThe organic layer was collected
  8. dry with materialdried over anhydrous magnesium sulfate
  9. distillationThe solvent was distilled off

Sources & evidence

ORD record
ord-2874295ab0af44b99ee377131981f9f5
Source dataset
uspto-grants-1977_01
Patent number
US04005084

Reaction notes

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