Sodium Hydroxide → Tetrahydrocannabinol

HRID 426095Notes

Reaction equation

HRID 426095 reaction equation
[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]1[CH:7]=[C:8]([OH:23])[C:9]2[C@@H:15]3[CH:16]=[C:17]([CH3:20])[CH2:18][CH2:19][C@H:14]3[C:13]([CH3:22])([CH3:21])[O:12][C:10]=2[CH:11]=1.[C@]12(CS([O-])(=O)=O)C(C)(C)C(CC1)CC2=O.[OH-].[Na+]>O.C(O)(C)(C)C>[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]1[CH:7]=[C:8]([OH:23])[C:9]2[C@@H:15]3[CH:16]=[C:17]([CH3:20])[CH2:18][CH2:19][C@H:14]3[C:13]([CH3:22])([CH3:21])[O:12][C:10]=2[CH:11]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86612161delta-9-tetrahydrocannabinol (1S)-10-camphorsulfonate

Product 1

HCID 16078Tetrahydrocannabinol

Reagents, catalysts & solvents 2

HCID 962WaterSolvent3×HCID 6386tert-ButanolSolvent2×

Conditions

Temperature
70 °C

Procedure

To a mechanically stirred slurry of crystalline purified delta-9-tetrahydrocannabinol (1S)-10-camphorsulfonate (1.1 g, 2.1 mmol) in water (3.6 mL) and t-butanol (7.4 mL) under argon, was added a mixture of sodium hydroxide (0.83 g, 21 mmol) in water (7.4 mL) and t-butanol (15 mL). The slurry was heated to 70° C. over 2 h, at which point the HPLC analysis showed the hydrolysis to be complete. The reaction mixture was cooled to ambient temperature and diluted with water (11 mL) and extracted with heptane (11 mL). The heptane solution was washed with water (2×6 mL). The heptane solution was concentrated under reduced pressure and the residue was dissolved in ethanol (5 mL). The ethanol solution was filtered through a 0.45 micron filter. HPLC analysis showed 99.2% delta-9-tetrahydrocannabinol and 0.49% cis-delta-9-tetrahydrocannabinol. (Agilent Technologies (Wilmington, Del.) Hypersil Gold, 4.6 mm×150 mm, isocratic MeOH/H2O/THF (71:24:5) mixture at 1 mL/min flow rate, 228 nm, delta-9-tetrahydrocannabinol rt=18.9 min, cis-delta-9-tetrahydrocannabinol rt=17.7 min). This solution was stored under an argon atmosphere and in the freezer until it was carried into the next step.

Workup

  1. additionwas added
  2. customthe hydrolysis
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. extractionextracted with heptane (11 mL)
  5. washThe heptane solution was washed with water (2×6 mL)
  6. concentrationThe heptane solution was concentrated under reduced pressure
  7. dissolutionthe residue was dissolved in ethanol (5 mL)
  8. filtrationThe ethanol solution was filtered through a 0.45 micron
  9. filtrationfilter
  10. custom(Agilent Technologies (Wilmington, Del.) Hypersil Gold, 4.6 mm×150 mm, isocratic MeOH/H2O/THF (71:24:5) mixture at 1 mL/min flow rate, 228 nm, delta-9-tetrahydrocannabinol rt=18.9 min, cis-delta-9-tetrahydrocannabinol rt=17.7 min)

Sources & evidence

ORD record
ord-ca374961979243c1bccc965d39def5bf
Source dataset
uspto-grants-2012_01
Patent number
US08106244B2

Reaction notes

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