Ethanolamine → Dihydrothebaine

HRID 920597Notes

Reaction equation

HRID 920597 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)C>[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 5324289Thebaine3×

Product 1

HCID 5486617DihydrothebaineYield 91.9%

Reagents, catalysts & solvents 1

HCID 79001-Methoxy-2-propanolSolvent2×

Conditions

Temperature
108 °C

Procedure

Thebaine (500.0 g containing 24.4 wt % water, 378.0 g dry basis, 1.21 mol, 1.0 equiv) is placed in a mixture of 1-methoxy-2-propanol (1304.2 g) and ethanolamine (130.6 g, 2.13 mol, 1.76 equiv) and is heated to 108±2° C. to give almost a complete solution. In another vessel, p-toluenesulfonylhydrazide (PTSH) (480.0 g, 2.57 mol, 2.12 equiv) is dissolved in a mixture of ethanolamine (960.1 g, 15.72 mol, 13.0 equiv) and 1-methoxy-2-propanol (80.1 g) and held at 20-25° C. The PTSH solution is then added slowly to the thebaine mixture at such a rate that the batch temperature remains in the range 108±2° C. and the gas evolution vents safely. After the complete addition, the reaction mixture is allowed to agitate at 108±2° C. and is monitored for reaction completion 0.3 area % thebaine remaining) by in-process HPLC analysis. On completion, the batch is cooled to 15±5° C. Water (1200 g) is then charged to the batch while maintaining the batch temperature at ≦30° C. The resulting slurry is stirred and further cooled to 5±3° C. and held for a minimum of 0.5 to 1 hours. The product is collected by filtration, washed with water (2400 g) and then dried at 55±5° C. to a constant weight to give 8,14-dihydrothebaine (yield, 348.4 g, 91.6% yield; purity, 99.2 area % by HPLC). The process described here in Example 1 is shown schematically in FIG. 1.

Workup

  1. customto give almost a complete solution
  2. customheld at 20-25° C
  3. customremains in the range 108±2° C.
  4. additionAfter the complete addition
  5. temperatureOn completion, the batch is cooled to 15±5° C
  6. temperaturewhile maintaining the batch temperature at ≦30° C
  7. stirringThe resulting slurry is stirred
  8. temperaturefurther cooled to 5±3° C.
  9. customheld for a minimum of 0.5 to 1 hours
  10. filtrationThe product is collected by filtration
  11. washwashed with water (2400 g)
  12. customdried at 55±5° C. to a constant weight

Sources & evidence

ORD record
ord-8d7f2e3c7a2041e1b851fd07798a8fb8
Source dataset
uspto-grants-2016_03
Patent number
US09273060B2

Reaction notes

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