Sulfuric Acid → (R)-Aminoglutethimide

HRID 2258419Notes

Reaction equation

HRID 2258419 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]#[N:17])([CH2:14][CH3:15])[CH2:9][CH2:10][C:11](O)=[O:12])=[CH:4][CH:3]=1.[OH:18]S(O)(=O)=O.[OH-].[Na+]>C(O)(=O)C>[CH3:15][CH2:14][C@@:8]1([C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=2)[C:16](=[O:18])[NH:17][C:11](=[O:12])[CH2:10][CH2:9]1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 22921469HCID 22921469, compound

Product 1

HCID 86488(R)-AminoglutethimideYield 97%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
60 °C

Procedure

4-(4-Aminophenyl)-4-cyanohexanoic acid (Example 9; 1.8 g, 7.7 mmol), enriched in the (R)-enantiomer, was dissolved in glacial acetic acid (6.0 ml) contained in a 25 ml round-bottomed flask. The resulting mixture was heated to 60° C. with the aid of an oil bath followed by dropwise addition of conc. H2SO4 (3.0 ml). The solution was then heated to 100° C. and maintained there for 30 minutes before pouring onto ice (100 g). The pH is adjusted to 6 using 5M NaOH followed by extraction with dichloromethane (3×200 ml). The extracts were pooled, dried (over MgSO4) and concentrated under reduced pressure, giving (R)-aminoglutethimide (1.75 g, 97%) as a brown oil. Chiral HPLC analysis (Chiralcel OJ column; mobile phase 1:1 n-heptane-isopropanol) indicated an ee of 78%.

Workup

  1. customcontained in a 25 ml round-bottomed flask
  2. temperatureThe solution was then heated to 100° C.
  3. temperaturemaintained there for 30 minutes
  4. additionbefore pouring onto ice (100 g)
  5. extractionfollowed by extraction with dichloromethane (3×200 ml)
  6. dry with materialdried (over MgSO4)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d6174773009f41828ed9aa7166f82a31
Source dataset
uspto-grants-1997_08
Patent number
US05661014

Reaction notes

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