4,4-Difluoropiperidine hydrochloride → HCID 16722359, compound

HRID 1983180Notes

Reaction equation

I[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([C:13]3[C:14]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[N:15][O:16][C:17]=3[CH3:18])=[N:11][N:12]=2)=[CH:4][CH:3]=1.CC(C)([O-])C.[Na+].Cl.[F:32][C:33]1([F:39])[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1>C1(C)C=CC=CC=1>[F:32][C:33]1([F:39])[CH2:38][CH2:37][N:36]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3[O:9][C:10]([C:13]4[C:14]([C:19]5[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=5)=[N:15][O:16][C:17]=4[CH3:18])=[N:11][N:12]=3)=[CH:4][CH:3]=2)[CH2:35][CH2:34]1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 2-(4-iodo-phenyl)-5-(5-methyl-3-phenyl-isoxazol-4-yl)-[1,3,4]oxadiazole (200 mg, 0.47 mmol) in toluene (2 mL) were added under an atmosphere of nitrogen 2-(dicyclohexylphosphino)biphenyl (15 mg, 0.04 mmol), tris(dibenzylideneacetone)di-palladium (0) chloroform complex (15 mg, 0.01 mmol), sodium tert-butoxide (107 mg, 1.12 mmol) and 4,4-difluoropiperidine hydrochloride (88 mg, 0.56 mmol). The reaction mixture was stirred for 1 h at 100° C. and was extracted with water (20 mL) and ethyl acetate (20 mL). The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine. Drying over sodium sulfate and purification by chromatography (SiO2, heptane:ethyl acetate=80:20 to 50:50) afforded the title compound (138 mg, 70%) as a light yellow solid. MS: m/e=423.3 [M+H]+.

Workup

extractionwas extracted with water (20 mL) and ethyl acetate (20 mL)
extractionThe aqueous layer was extracted with ethyl acetate
washthe combined organic layers were washed with brine
dry with materialDrying over sodium sulfate and purification by chromatography (SiO2, heptane:ethyl acetate=80:20 to 50:50)

Sources & evidence

ORD record: ord-c17becd5f7b6465ca23b06617581ba9b
Source dataset: uspto-grants-2009_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07541372B2

Reaction notes

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