Trityl chloride → (S)-4-trityl-2-hydroxymethylmorpholine

HRID 362960Notes

Reaction equation

HRID 362960 reaction equation
C([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][OH:15])[CH2:9]1)C1C=CC=CC=1.Cl.C(O)C.[C:20](Cl)([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(OC(C)C)(C)C>C(O)C.C(Cl)Cl.[C].[Pd].C(N(CC)CC)C.CO>[C:20]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][OH:15])[CH2:9]1)([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

10

Reactant 4

HCID 6456Trityl chlorideHCID 7914Diisopropyl EtherHCID 736507(S)-(4-benzylmorpholin-2-yl)methanolHCID 21887872Ethanol hydrochloride

Product 1

HCID 10570464(S)-4-trityl-2-hydroxymethylmorpholineYield 44.6%

Reagents, catalysts & solvents 5

HCID 178418390HCID 178418390, compoundCatalyst2×HCID 702EthanolSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

3.5 g of (S)-4-benzyl-2-hydroxymethylmorpholine was dissolved in 5 ml of ethanol. To the solution was added 5 ml of a 5.9N dry hydrogen chloride-ethanol solution with ice cooling. The resulting mixture was stirred for 10 minutes at the same temperature. Thereto was added a mixture of 500 mg of 5% palladium-carbon and 10 ml of methanol. The resulting mixture was subjected to hydrogenation for 3 hours at 40° C. After the completion of the reaction, palladium-carbon was removed by filtration. The solvent was removed by distillation under reduced pressure to obtain a yellow oily product. To the oily product were added 20 ml of dry methylene chloride and 4.7 ml of triethylamine. The resulting mixture was stirred at room temperature for 30 minutes. Thereto was dropwise added a solution of 4.7 g of trityl chloride dissolved in 10 ml of methylene chloride in 20 minutes, with ice cooling. The mixture was stirred at room temperature for 3 hours and added to 50 ml of ice water. The organic layer was separated and 20 ml of water was added thereto. The resulting mixture was adjusted to pH 12 with a 1N aqueous sodium hydroxide solution. The organic layer was separated and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure to obtain a yellow oily product. The oily product was mixed with 10 ml of diisopropyl ether. The resulting crystals were collected by filtration to obtain 2.7 g of (S)-4-trityl-2-hydroxymethylmorpholine.

Workup

  1. additionThereto was added
  2. waitThe resulting mixture was subjected to hydrogenation for 3 hours at 40° C
  3. customwas removed by filtration
  4. customThe solvent was removed by distillation under reduced pressure
  5. customto obtain a yellow oily product
  6. stirringThe resulting mixture was stirred at room temperature for 30 minutes
  7. stirringThe mixture was stirred at room temperature for 3 hours
  8. customThe organic layer was separated
  9. addition20 ml of water was added
  10. customThe organic layer was separated
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customThe solvent was removed by distillation under reduced pressure
  13. customto obtain a yellow oily product
  14. filtrationThe resulting crystals were collected by filtration

Sources & evidence

ORD record
ord-6927b0c552ba4958973632a3fb60b536
Source dataset
uspto-grants-1999_02
Patent number
US05872117

Reaction notes

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