Hydrochloric Acid → Bexarotene

HRID 356719Notes

Reaction equation

HRID 356719 reaction equation
[CH3:1][C:2]1[C:3]([C:16]([C:18]2[CH:27]=[CH:26][C:21]([C:22]([O:24]C)=[O:23])=[CH:20][CH:19]=2)=[CH2:17])=[CH:4][C:5]2[C:6]([CH3:15])([CH3:14])[CH2:7][CH2:8][C:9]([CH3:13])([CH3:12])[C:10]=2[CH:11]=1.[OH-].[K+].Cl>CO>[CH3:1][C:2]1[C:3]([C:16]([C:18]2[CH:27]=[CH:26][C:21]([C:22]([OH:24])=[O:23])=[CH:20][CH:19]=2)=[CH2:17])=[CH:4][C:5]2[C:6]([CH3:15])([CH3:14])[CH2:7][CH2:8][C:9]([CH3:12])([CH3:13])[C:10]=2[CH:11]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 10384066Methyl 4-(1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)vinyl)benzoate

Product 1

HCID 82146Bexarotene

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

To a suspension of the ester 32 (0.058 g, 0.16 mmol) in 75% aqueous methanol (2 mL) was added one pellet of potassium hydroxide (0.1 g). The mixture was stirred at 70° C. for 1 h during which time the material dissolved. The solution was cooled to room temperature, acidified with 1N aqueous hydrochloric acid, and then extracted with 80% ethyl acetate/hexane. The combined organic layers were dried over anhydrous MgSo4, filtered, and concentrated to afford a white solid. Recrystallization from dichloromethane/hexane afforded the desired acid 33 as a white, crystalline solid (42 mg, 91%): m.p. 230°-231° C. The structure of the product was also confirmed using IR, 1H NMR and mass spectroscopy.

Workup

  1. dissolutiondissolved
  2. temperatureThe solution was cooled to room temperature
  3. extractionextracted with 80% ethyl acetate/hexane
  4. customThe combined organic layers were dried over anhydrous MgSo4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto afford a white solid
  8. customRecrystallization from dichloromethane/hexane

Sources & evidence

ORD record
ord-f1d2e81236fe4b1a9391f0be8a00da42
Source dataset
uspto-grants-1998_11
Patent number
US05837725

Reaction notes

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