Hydrochloric Acid → 6-fluoro-2-methyl-3-[(3S,9aR)-octahydropyrazino[2,1-c][1,4]oxazin-3-yl]benzonitrile hydrochloride
Reaction equation
[C:1]([C:3]1[C:4]([CH3:27])=[C:5]([C@@H:10]2[O:15][CH2:14][C@H:13]3[CH2:16][N:17](C(OC(C)(C)C)=O)[CH2:18][CH2:19][N:12]3[CH2:11]2)[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].[ClH:28]>CC(O)C>[ClH:28].[F:9][C:8]1[C:3]([C:1]#[N:2])=[C:4]([CH3:27])[C:5]([C@@H:10]2[O:15][CH2:14][C@H:13]3[CH2:16][NH:17][CH2:18][CH2:19][N:12]3[CH2:11]2)=[CH:6][CH:7]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 50 °C
Procedure
(3S,9aR)-tert-Butyl 3-(3-cyano-4-fluoro-2-methylphenyl)hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate (158.8 g, 423.0 mmol) was suspended with 318 mL of 2-propanol. The resulting slurry was treated with HCl solution in 2-propanol (5.5 M, 1000 mL, 5499 mmol), and the mixture was heated to 50° C. for 2 hours. The mixture was concentrated to remove approximately 400 mL of 2-propanol, then was cooled to rt and agitated overnight. The mixture was filtered to collect the solid product and the wet cake was washed with 50 mL of 2-propanol. The filter cake was dried under vacuum for two days at 40° C. with nitrogen bleed to afford the title compound.
Workup
- concentrationThe mixture was concentrated
- customto remove approximately 400 mL of 2-propanol
- temperaturewas cooled to rt
- filtrationThe mixture was filtered
- customto collect the solid product
- washthe wet cake was washed with 50 mL of 2-propanol
- customThe filter cake was dried under vacuum for two days at 40° C. with nitrogen
Sources & evidence
- ORD record
- ord-d9582425c8d1426b98ef9674598d21a0
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09206199B2
Reaction notes
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