Water → Dihydrothebaine

HRID 920602Notes

Reaction equation

HRID 920602 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.N1CCOCC1.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 962WaterHCID 8083Morpholine2×HCID 5324289Thebaine2×

Product 1

HCID 5486617DihydrothebaineYield 89.1%

Reagents, catalysts & solvents 1

HCID 79001-Methoxy-2-propanolSolvent2×

Conditions

Temperature
112.5 °C

Procedure

Thebaine (4.0 g dry basis, 12.9 mmol) is placed in a mixture of 1-methoxy-2-propanol (13.0 g) and morpholine (1.3 g, 14.9 mmol, 1.16 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 morpholine (9.6 g, 110.2 mmol, 8.54 equiv) and 1-methoxy-2-propanol (0.8 g) and the solution added in portions to the Thebaine mixture over 1 h 10 min while maintaining the batch temperature in the range 110 to 115° C. The reaction mixture is held at 110 to 114° C. for 1.75 h then cooled to less than 20° C. and water (24 g) added. The resulting slurry (pH 9.7) is stirred and 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 (3.59 g, 89.1% yield; 98.7 area % purity by HPLC).

Workup

  1. temperaturethen cooled to less than 20° 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-97a7ff2494064d708de0b58ced176a64
Source dataset
uspto-grants-2016_03
Patent number
US09273060B2

Reaction notes

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