4-Methylmorpholine → HCID 13066725, compound

HRID 358020Notes

Reaction equation

HRID 358020 reaction equation
CN1CCOCC1.[C:8]([S:16][CH2:17][CH2:18][C:19]([N:21]1[C@H:25]([C:26](O)=[O:27])[CH2:24][S:23][C@@H:22]1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[OH:35])=[O:20])(=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(Cl)(=O)OCC(C)C.Cl.[NH2:45][OH:46].[OH-].[Na+]>CO.O1CCCC1>[C:8]([S:16][CH2:17][CH2:18][C:19]([N:21]1[C@H:25]([C:26]([NH:45][OH:46])=[O:27])[CH2:24][S:23][C@@H:22]1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[OH:35])=[O:20])(=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 14798Sodium HydroxideHCID 62365Isobutyl chloroformateHCID 443297Hydroxyamine hydrochlorideHCID 12915689HCID 12915689, compound

Product 1

HCID 13066725HCID 13066725, compoundYield 46.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

3.1 g of N--methylmorpholine is added to 180 ml of dry tetrahydrofuran solution of 12.5 g of (2R,4R)--3--(S--benzoyl--3--mercaptopropionyl) --2--(2--hydroxyphenyl)--4--thiazolidine--carboxylic acid. To the reaction mixture, 4.1 g of isobutyl chlorocarbonate is added dropwise while stirring under ice-cooling and further stirred for 30 minutes at the same temperature. To this suspension, 120 ml of methanol solution containing 6.3 g of hydroxylamine hydrochloride and 3.6 g of sodium hydroxide is added dropwise, and stirred for 2 hours by gradually restoring the room temperature. The solvent is removed in vacuo, and N hydrochloric acid is added to the resulting residue. Separated oil is extracted with ethyl acetate, and the organic layer is washed with saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent is removed in vacuo and the resulting oily residue is purified by silica gel coulumn chromatography to give 6.0 g of the titled compound.

Workup

  1. temperaturecooling
  2. stirringfurther stirred for 30 minutes at the same temperature
  3. additionis added dropwise
  4. stirringstirred for 2 hours
  5. customthe room temperature
  6. customThe solvent is removed in vacuo, and N hydrochloric acid
  7. additionis added to the resulting residue
  8. customSeparated oil
  9. extractionis extracted with ethyl acetate
  10. washthe organic layer is washed with saturated sodium chloride solution
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customThe solvent is removed in vacuo
  13. customthe resulting oily residue is purified by silica gel coulumn chromatography

Sources & evidence

ORD record
ord-da64e97c408641469e1ab232d5e1eb0a
Source dataset
uspto-grants-1984_08
Patent number
US04464371

Reaction notes

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