Diethyl Ether → 4-[(s)-1-(2-Chloropyridin-4-yl)ethyl]-6,6-dimethylmorpholine-2,3-dione

HRID 1436131Notes

Reaction equation

HRID 1436131 reaction equation
Cl([O-])(=O)(=O)=[O:2].[Li+].[Cl:7][C:8]1[CH:13]=[C:12]([C@@H:14]([NH2:16])[CH3:15])[CH:11]=[CH:10][N:9]=1.[CH3:17][C:18]1(O[CH2:20]1)[CH3:19].[OH-:22].[Na+].CC[O:26][CH2:27][CH3:28]>>[Cl:7][C:8]1[CH:13]=[C:12]([C@@H:14]([N:16]2[CH2:20][C:18]([CH3:17])([CH3:19])[O:22][C:27](=[O:26])[C:28]2=[O:2])[CH3:15])[CH:11]=[CH:10][N:9]=1

Participants

6

Reactant 5

HCID 3283Diethyl EtherHCID 11208Isobutylene oxideHCID 14798Sodium HydroxideHCID 23665649Lithium perchlorateHCID 50999258(S)-2-Chloro-4-(1-amino)ethylpyridine

Product 1

HCID 876525354-[(s)-1-(2-Chloropyridin-4-yl)ethyl]-6,6-dimethylmorpholine-2,3-dione

Conditions

Temperature
0 °C

Procedure

Lithium perchlorate (10.2 g) was added to a solution of (S)-1-(2-chloropyridin-4-yl)ethylamine obtained in Example 51 (1 g) in an ether (18.5 mL), and the reaction solution was stirred for five minutes. Isobutylene oxide (1.7 mL) was added to the reaction solution, which was then stirred overnight. A 5 N sodium hydroxide solution was added to the reaction solution at 0° C., followed by extraction with chloroform. The organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. Dichloromethane (20 mL) and pyridine (20 mL) were added to the residue, and the reaction solution was cooled to 0° C. Oxalyl chloride (669 μL) was added to the reaction solution, which was then stirred at 0° C. for one hour and at room temperature for one hour. Oxalyl chloride (0.4 mL) was added to the reaction solution, which was further stirred for one hour. The solvent was evaporated under reduced pressure. Water and ethyl acetate were added to the residue, and the organic layer was separated. The organic layer was dried over magnesium sulfate, and the residue was purified by silica gel column chromatography (Chromatorex; elution solvent: heptane-ethyl acetate) to obtain the title compound (1.07 g). The property values of the compound are as follows.

Workup

  1. stirringwas then stirred overnight
  2. extractionfollowed by extraction with chloroform
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. additionDichloromethane (20 mL) and pyridine (20 mL) were added to the residue
  6. additionOxalyl chloride (669 μL) was added to the reaction solution, which
  7. stirringwas then stirred at 0° C. for one hour and at room temperature for one hour
  8. additionOxalyl chloride (0.4 mL) was added to the reaction solution, which
  9. stirringwas further stirred for one hour
  10. customThe solvent was evaporated under reduced pressure
  11. additionWater and ethyl acetate were added to the residue
  12. customthe organic layer was separated
  13. dry with materialThe organic layer was dried over magnesium sulfate
  14. customthe residue was purified by silica gel column chromatography (Chromatorex; elution solvent: heptane-ethyl acetate)

Sources & evidence

ORD record
ord-73d39f2db2844633addb2c06b1c95f47
Source dataset
uspto-grants-2009_11
Patent number
US07618960B2

Reaction notes

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