Ethanolamine → Dihydrothebaine

HRID 920604Notes

Reaction equation

HRID 920604 reaction equation
[CH3:1][N:2]1[C@@H:18]2[CH2:19][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([O:20][CH3:21])=[CH:15][CH:16]=[C:17]2[C@:5]5([C:6]=34)[CH2:4][CH2:3]1.C(CN)O.O>COCC(O)CO>[CH3:1][N:2]1[C@@H:18]2[CH2:19][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([O:20][CH3:21])=[CH:15][CH2:16][C@@H:17]2[C@:5]5([C:6]=34)[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 700Ethanolamine2×HCID 962WaterHCID 5324289Thebaine2×

Product 1

HCID 5486617DihydrothebaineYield 81%

Reagents, catalysts & solvents 1

HCID 928223-Methoxy-1,2-propanediolSolvent2×

Conditions

Temperature
20 °C

Procedure

Thebaine (4.0 g dry basis, 12.9 mmol) is placed in a mixture of 3-methoxy-1,2-propanediol (13.0 g) and ethanolamine (1.3 g, 21.3 mmol, 1.65 equiv) and is heated at 110 to 114° C. p-Toluenesulfonylhydrazide (4.8 g, 25.8 mmol, 2.0 equiv) is dissolved at 15 to 25° C. in a mixture of ethanolamine (9.6 g, 157.2 mol, 12.2 equiv) and 3-methoxy-1,2-propanediol (0.8 g) and the solution is added in portions to the thebaine mixture over 1.25 hours. The reaction mixture is held at 110 to 114° C. for 1.25 hours then cooled to 15 to 25° C. and water (24 g) added while maintaining the batch temperature at ≦30° C. The resulting slurry (pH 10.9) is stirred, further cooled to 0 to 5° C. and then filtered. The product is washed with water (3×8 g) and dried at 40° C. to a constant weight to give 8,14-dihydrothebaine (3.26 g, 81.0% yield; 97.0 area % purity by HPLC).

Workup

  1. temperaturewhile maintaining the batch temperature at ≦30° C
  2. temperaturefurther cooled to 0 to 5° C.
  3. filtrationfiltered
  4. washThe product is washed with water (3×8 g)
  5. customdried at 40° C. to a constant weight

Sources & evidence

ORD record
ord-a57f33d8d2f843a0bc7f885ef4226b57
Source dataset
uspto-grants-2016_03
Patent number
US09273060B2

Reaction notes

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