Trifluoromethanesulfonic acid → Morphine

HRID 1268148Notes

Reaction equation

HRID 1268148 reaction equation
C([O:4][C:5]1[CH:6]=[CH:7][C:8]2[CH2:9][C@H:10]3[N:22]([CH3:23])[CH2:21][CH2:20][C@:16]45[C:17]=2[C:18]=1[O:19][C@H:15]4[C@@H:14]([OH:24])[CH:13]=[CH:12][C@@H:11]35)(=O)C.FC(F)(F)S(O)(=O)=O.IN1C(=O)CCC1=O>ClCCl>[CH:7]1[C:8]2[CH2:9][C@H:10]3[N:22]([CH2:21][CH2:20][C@@:16]45[C@H:11]3[CH:12]=[CH:13][C@H:14]([OH:24])[C@@H:15]4[O:19][C:18]([C:17]=25)=[C:5]([OH:4])[CH:6]=1)[CH3:23]

Participants

5

Reactant 3

HCID 62406Trifluoromethanesulfonic acidHCID 120273N-IodosuccinimideHCID 54625043-Monoacetylmorphine

Product 1

HCID 5288826Morphine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-15 °C

Procedure

A suspension of 4.2 g (6.9 mmol) of Thioglycoside [14], 1.5 g (4.6 mmol) of freshly prepared, vacuum-dried 3-O-Acetylmorphine and 6.0 g 3 Å Molecular Sieves in 60 mL Dichloromethane was stirred at room temperature for 30 min and cooled to −15° C. by an ice-salt-acetone bath. Trifluoromethanesulfonic acid (TfOH) (1.0 g, 6.7 mmol) was added dropwise while keeping the temperature at below −10° C. and then N-Iodosuccinimide (NIS) (1.55 g, 6.9 mmol) was added in three portions. The resulted mixture was stirred for 4 hours at −5° C. and for an additional 30 min. at room temperature. Then the reaction mixture was diluted with Dichloromethane, filtered through Celite, stirred for 30 min with saturated aq. Sodium Hydrogen Carbonate solution (60 mL) and the aqueous layer was separated. The organic layer was washed twice with 60 mL portions of Sodium Thiosulphate saturated aqueous solution and water. The combined aqueous solution was washed with 60 mL of Dichloromethane. Combined organic solution was dried over Sodium Sulfate anhydrous, filtered and evaporated under reduced pressure. After separation on Silica Gel collumn compound [13] 1.93 g (51%) and 0.4 g of Morphine were obtained.

Workup

  1. customof freshly prepared
  2. customat below −10° C.
  3. filtrationfiltered through Celite
  4. stirringstirred for 30 min with saturated aq. Sodium Hydrogen Carbonate solution (60 mL)
  5. customthe aqueous layer was separated
  6. washThe organic layer was washed twice with 60 mL portions of Sodium Thiosulphate saturated aqueous solution and water
  7. washThe combined aqueous solution was washed with 60 mL of Dichloromethane
  8. dry with materialCombined organic solution was dried over Sodium Sulfate anhydrous
  9. filtrationfiltered
  10. customevaporated under reduced pressure
  11. customAfter separation on Silica Gel collumn compound [13] 1.93 g (51%)

Sources & evidence

ORD record
ord-18dc3081d09a4500b56c216ad0504fee
Source dataset
uspto-grants-2003_04
Patent number
US06555665B1

Reaction notes

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