Diethyl Ether → (2R,3R)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol

HRID 1582234Notes

Reaction equation

HRID 1582234 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([C@@:9]2([OH:18])[O:14][CH2:13][C:12]([CH3:16])([CH3:15])[NH:11][C@@H:10]2[CH3:17])[CH:6]=[CH:7][CH:8]=1.C(OCC)C.[OH-].[Na+]>O>[Cl:2][C:3]1[CH:4]=[C:5]([C@@:9]2([OH:18])[O:14][CH2:13][C:12]([CH3:15])([CH3:16])[NH:11][C@@H:10]2[CH3:17])[CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 14798Sodium HydroxideHCID 9943907Bupropion Morpholinol (2R,3R)-Isomer2×

Product 1

HCID 9943908(2R,3R)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

(+/−)-(2R*,3R*)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol hydrochloride may be converted back to its free base by the following process. A 3.0 g sample of (+/−)-(2R*,3R*)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol hydrochloride was dissolved in water (100 mL) and diethyl ether was added (200 mL). The mixture was chilled in an ice bath and the pH was adjusted to >10 with 1.0N aqueous sodium hydroxide. After stirring for 30 min., the phases were separated and the aqueous phase was extracted with diethyl ether. The combined diethyl ether extracts were dried (Na2SO4) and concentrated in vacuo to give 2.6 g of (+/−)-(2R*,3R*)-2-(3-chlorophenyl)-3,5,5-trimethyl-2-morpholinol as a white solid. This was used without further purification for the chiral chromatography described below.

Workup

  1. temperatureThe mixture was chilled in an ice bath
  2. customthe phases were separated
  3. extractionthe aqueous phase was extracted with diethyl ether
  4. dry with materialThe combined diethyl ether extracts were dried (Na2SO4)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-588f25a0d5df45159f65ab2cea46353a
Source dataset
uspto-grants-2004_05
Patent number
US06734213B2

Reaction notes

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