Water → HCID 20289411, compound

HRID 1414000Notes

Reaction equation

HRID 1414000 reaction equation
[C:1]1([CH2:7][O:8][CH2:9][CH:10]2[CH2:15][N:14]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:13][CH:12]([CH2:23][OH:24])[O:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[CH2:26][C:27]([N:29]([CH2:33][CH2:34][CH3:35])[CH2:30][CH2:31][CH3:32])=[O:28].[H-].[Na+].O>CS(C)=O>[C:1]1([CH2:7][O:8][CH2:9][CH:10]2[CH2:15][N:14]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:13][CH:12]([CH2:23][O:24][CH2:26][C:27]([N:29]([CH2:33][CH2:34][CH3:35])[CH2:30][CH2:31][CH3:32])=[O:28])[O:11]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 2196472-chloro-N,N-dipropylacetamideHCID 20289417HCID 20289417, compound

Product 1

HCID 20289411HCID 20289411, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

A mixture of 4.9 g (0.015 mole) of 6-[(phenylmethoxy)methyl]-4-(phenylmethyl)-2-morpholinemethanol and 2.84 g (0.016 mole) of 2-chloro-N,N-dipropylacetamide are dissolved in 100 ml of dry DMSO and the mixture stirred at room temperature under nitrogen. Slowly, 0.88 g of sodium hydride (0.0183 mole, 50% oil dispersion) is added to the DMSO mixture and the reaction allowed to stir at ambient temperature (22°). After stirring for 10 minutes, an exothermic reaction begins to take place and an ice-bath is used to maintain the reaction temperature below 30°. After stirring for 1/2 hour, the ice-bath is removed and the reaction allowed to stir at room temperature for 18 hours. The excess NaH is destroyed by adding 5 ml of methanol and the entire reaction mixture is then poured into 400 ml of water. The product is extracted and washed with 6×300 ml portions of water. The product is then extracted with 3×125 ml portions of chloroform. The CHCl3 extracts are combined and washed with 6×300 ml portions of water. The CHCl3 layer is separated and dried over anhydrous Na2SO4 overnight. The CHCl3 is removed in vacuo yielding the crude product as a dark oil. The resulting oil is purified on a neutral Alumina III column (200 g), eluting with 2% methanol/chloroform, yielding 4.6 g (69%) of the desired product, 2-[[6-[(phenylmethoxy)methyl]-4-(phenylmethyl)-2-morpholinyl]methoxy]-N,N-dipropylacetamide.

Workup

  1. stirringto stir at ambient temperature (22°)
  2. stirringAfter stirring for 10 minutes
  3. customan exothermic reaction
  4. temperatureto maintain the reaction temperature below 30°
  5. stirringAfter stirring for 1/2 hour
  6. customthe ice-bath is removed
  7. stirringto stir at room temperature for 18 hours
  8. customThe excess NaH is destroyed
  9. additionby adding 5 ml of methanol
  10. customthe entire reaction mixture
  11. extractionThe product is extracted
  12. washwashed with 6×300 ml portions of water
  13. extractionThe product is then extracted with 3×125 ml portions of chloroform
  14. washwashed with 6×300 ml portions of water
  15. customThe CHCl3 layer is separated
  16. dry with materialdried over anhydrous Na2SO4 overnight
  17. customThe CHCl3 is removed in vacuo
  18. customyielding the crude product as a dark oil
  19. customThe resulting oil is purified on a neutral Alumina III column (200 g)
  20. washeluting with 2% methanol/chloroform

Sources & evidence

ORD record
ord-c705d5191a08499c95f2174b3ef5f1ff
Source dataset
uspto-grants-1981_02
Patent number
US04252801

Reaction notes

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