Hydrochloric Acid → Morphine

HRID 1921148Notes

Reaction equation

HRID 1921148 reaction equation
S(O)(O)(=O)=O.[CH:6]1[C:22]2[CH2:21][C@H:20]3[N:23]([CH2:25][CH2:26][C@@:12]45[C@H:19]3[CH:18]=[CH:17][C@H:15]([OH:16])[C@@H:13]4[O:14][C:10]([C:11]=25)=[C:8]([OH:9])[CH:7]=1)[CH3:24].C([O-])([O-])=O.[K+].[K+].C(Cl)Cl.Cl>O>[CH:6]1[C:22]2[CH2:21][C@H:20]3[N:23]([CH2:25][CH2:26][C@@:12]45[C@H:19]3[CH:18]=[CH:17][C@H:15]([OH:16])[C@@H:13]4[O:14][C:10]([C:11]=25)=[C:8]([OH:9])[CH:7]=1)[CH3:24]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 546428064-31-3

Product 1

HCID 5288826MorphineYield 56%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Morphine sulfate USP from Spectrum (510 mg) was dissolved in water (70 ml). The solution was then basified to pH 10 using aqueous K2CO3 to give a white suspension. To the white suspension DCM (dichloromethane, 50 ml) was added, but failed to dissolve the solid. The mixture was made acidic with 1M HCl to result in clear biphasic solution. The organic phase was split off and the aqueous phase was carefully brought to pH 9.30 (monitored by a pH meter) using the same solution of K2CO3 as above. A white suspension resulted again. The heterogeneous mixture was extracted with DCM (5×25 ml) and an insoluble white solid contaminated both the organic and aqueous layers. The organic layer was dried with MgSO4, filtered and rotary evaporated to yield 160 mg of morphine free base (56% recovery). No additional product was recovered from the filter cake using MeOH, but another 100 mg was recovered from the aqueous phase by 2×50 ml extraction with EtOAc to give a combined yield of 260 mg (68%).

Workup

  1. customto give a white suspension
  2. dissolutionto dissolve the solid
  3. customto result in clear biphasic solution
  4. customThe organic phase was split off
  5. customA white suspension resulted again
  6. extractionThe heterogeneous mixture was extracted with DCM (5×25 ml)
  7. dry with materialThe organic layer was dried with MgSO4
  8. filtrationfiltered
  9. customrotary evaporated

Sources & evidence

ORD record
ord-1a538e1441994b4e9e9a17f9c952caa2
Source dataset
uspto-grants-2012_05
Patent number
US08173666B2

Reaction notes

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