1,3-Propanediamine → Dihydrothebaine

HRID 920605Notes

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)CCN.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: 105 °C

Procedure

Thebaine (4.0 g dry basis, 13 mmol) is placed in a mixture of 1-methoxy-2-propanol (13.0 g) and 1,3-propanediamine (1.6 g, 22 mmol, 1.66 equiv) and is heated at 105° C. A solution of p-toluenesulfonylhydrazide (4.8 g, 26 mmol, 2.0 equiv) in 1,3-propanediamine (9.6 g, 130 mmol, 9.96 equiv) is added in portions to the thebaine mixture at such a rate that the batch temperature is maintained in the range 105 to 110° C. The reaction mixture is held at 105 to 110° C. for 1 hour then cooled to room temperature and water (24 g) is added while maintaining the batch temperature at ≦30° C. The resulting slurry is stirred, further cooled to ˜2° 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 (3.80 g, 94.3% yield; 99.0 area % purity by HPLC)

Workup

temperatureis maintained in the range 105 to 110° C
temperaturethen cooled to room temperature
temperaturewhile maintaining the batch temperature at ≦30° C
temperaturefurther cooled to ˜2° C.
filtrationfiltered
washThe product is washed with water (3×8 g)
customdried at 40° C. to a constant weight

Sources & evidence

ORD record: ord-5f154a33add64f8180476aa7b92b64ba
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273060B2

Reaction notes

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