Hydrochloric Acid → HCID 75201371, compound

HRID 1051398Notes

Reaction equation

HRID 1051398 reaction equation
[F:1][C:2]([F:35])([F:34])[CH:3]([CH2:21][C:22]1[O:23][C:24]([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)=[N:25][N:26]=1)[CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH:7]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[CH2:6]1.[ClH:36]>CCOCC.CCCCCC.O1CCOCC1>[ClH:36].[F:35][C:2]([F:1])([F:34])[CH:3]([CH2:21][C:22]1[O:23][C:24]([C:27]2[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=2)=[N:25][N:26]=1)[CH2:4][N:5]1[CH2:10][CH2:9][O:8][CH:7]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([F:20])([F:19])[F:18])[CH:12]=2)[CH2:6]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 75201372HCID 75201372, compound

Product 1

HCID 75201371HCID 75201371, compound

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 21584099Diethylether hexaneSolvent

Procedure

To a 5 mL round-bottomed flask was added 4,4,4-trifluoro-3-((2-(3-(trifluoromethyl)phenyl)-morpholinomethyl)butanoic acid hydrochloride (100 mg, 260 μmol), 4-fluorobenzohydrazide (40.0 mg, 260 μmol) and POCl3 (1.99 g, 1.21 ml, 13.0 mmol). The reaction mixture was heated at reflux (110° C.) for 4 hr. The crude reaction mixture was allowed to cool to room temperature, poured into ice/water and made basic with a saturated Na2CO3 solution. The resulting mixture was extracted with ethyl acetate. The organic phase was washed with brine and H2O, dried over MgSO4, filtered and concentrated. The crude material was purified by flash chromatography (silica gel, 12 g, 0% to 40% ethyl acetate in CH2Cl2/hexane (1:1) to afford 4-{3,3,3-trifluoro-2-[5-(4-fluoro-phenyl)-[1,3,4]oxadiazol-2-ylmethyl]-propyl}-2-(3-trifluoromethyl-phenyl)morpholine as an oil (93 mg, 67%). 4-{3,3,3-Trifluoro-2-[5-(4-fluoro-phenyl)-[1,3,4]oxadiazol-2-ylmethyl]-propyl}-2-(3-trifluoromethyl-phenyl)morpholine (45 mg) was dissolved in ether/hexane, treated with 4N HCl in dioxane (0.2 ml) and concentrated to afford 48 mg of 4-{3,3,3-trifluoro-2-[5-(4-fluoro-phenyl)-[1,3,4]oxadiazol-2-ylmethyl]-propyl}-2-(3-trifluoromethyl-phenyl)morpholine hydrochloride as a white solid. LCMS MH+=504.

Workup

  1. concentrationconcentrated

Sources & evidence

ORD record
ord-443ebe6d430f48e9912b84495d54ae75
Source dataset
uspto-grants-2016_07
Patent number
US09388172B2

Reaction notes

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