Hydrochloric Acid → Dasotraline Hydrochloride

HRID 39620Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C@H:12]([NH:19]C(=O)C)[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].Cl>C(O)CC>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([C@H:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[C@H:12]([NH2:19])[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of trans-acetamide 4 (9.0 g, 26.9 mmol), n-propanol (45 mL) and 5M hydrochloric acid (45 mL) was refluxed for approximately 48 h (90-93° C.). During this time, the reaction temperature was maintained at ≧90° C. by periodically collecting the distillate until the reaction temperature was >92° C. Additional n-propanol was added periodically to maintain the solution at its original volume. After the hydrolysis was complete, the solution was slowly cooled to 0° C., resulting in a slurry, which was aged for one hour at 0° C. The reaction mixture was filtered, and the cake was washed with 1:1 methanol/water (20 mL), followed by t-butyl methyl ether (20 mL). The wet-cake was dried under vacuum at 45 to 50° C. to afford 7.0 g of the amine hydrochloride 5 (80% yield).

Workup

temperatureDuring this time, the reaction temperature was maintained at ≧90° C.
distillationby periodically collecting the distillate until the reaction temperature
customwas >92° C
additionAdditional n-propanol was added periodically
temperatureto maintain the solution at its original volume
customresulting in a slurry, which
filtrationThe reaction mixture was filtered
washthe cake was washed with 1:1 methanol/water (20 mL)
customThe wet-cake was dried under vacuum at 45 to 50° C.

Sources & evidence

ORD record: ord-e4dd0ed6209f4d7fbca7a29c7636b63a
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08524950B2

Reaction notes

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