Water → Dihydrothebaine

HRID 920599Notes

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(N)CN.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

Conditions

Temperature: 110 °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 ethylenediamine (1.3 g, 21.6 mmol, 1.68 equiv) and is heated to 110° C. p-Toluenesulfonylhydrazide (4.8 g, 25.8 mmol, 2.0 equiv) is dissolved at room temperature in a mixture of ethylenediamine (9.6 g, 159.7 mol, 12.4 equiv) and 1-methoxy-2-propanol (0.8 g) and the solution is added in portions to the thebaine mixture over 1 hour 20 minutes at such a rate that the batch temperature is maintained at ˜110° C. The reaction mixture is held at this temperature for 1 hour then cooled to room temperature and then water (24 g) is added while maintaining the batch temperature at ≦30° C. The resulting slurry (pH 11.4) is filtered and the product is washed with water (3×8 g) and dried at 40° C. to a constant weight to give 8,14-dihydrothebaine (3.68 g, 91.3% yield; 99.1 area % purity by HPLC).

Workup

temperaturethen cooled to room temperature
temperaturewhile maintaining the batch temperature at ≦30° C
filtrationThe resulting slurry (pH 11.4) is filtered
washthe product is washed with water (3×8 g)
customdried at 40° C. to a constant weight

Sources & evidence

ORD record: ord-7a42664ac771458097d36b7fb542b71e
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273060B2

Reaction notes

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