1-Trifluoroacetyl piperidine → HCID 86685867, compound
Reaction equation
I[C:2]1[CH:3]=[N:4][N:5]([CH2:7][CH2:8][CH2:9][CH2:10][C:11]([F:14])([F:13])[F:12])[CH:6]=1.C([Mg]Cl)(C)C.[F:20][C:21]([F:31])([F:30])[C:22](N1CCCCC1)=[O:23]>O1CCCC1>[F:20][C:21]([F:31])([F:30])[C:22]([C:2]1[CH:3]=[N:4][N:5]([CH2:7][CH2:8][CH2:9][CH2:10][C:11]([F:14])([F:13])[F:12])[CH:6]=1)=[O:23]Participants
Conditions
- Temperature
- -78 °C
Procedure
To a stirred solution of Intermediate 12A (460 mg, 1.446 mmol) in tetrahydrofuran (5 mL) at 0° C. was added isopropylmagnesium chloride (0.795 mL, 1.591 mmol) quickly. After 30 min, additional 0.25 eq of iPrMgCl was added and after 30 min, the mixture was cooled to −78° C. 2,2,2-Trifluoro-1-(piperidin-1-yl)ethanone (288 mg, 1.591 mmol) was added quickly and the reaction was warmed to rt and stirred for 3 h. The reaction was quenched with sat'd aq NH4Cl and diluted with EtOAc. The organic layer was washed with sat'd aq NH4Cl, dried over MgSO4, filtered and concentrated in vacuo. The crude product was purified by silica gel chromatography (40 g silica gel, eluted with 0-100% EtOAc in hexanes) to give the desired product (265 mg, 64%) as clear oil. 1H NMR (500 MHz, CDCl3) δ 8.08 (s, 2H), 4.22 (t, J=7.0 Hz, 2H), 2.07-2.20 (m, 2H), 1.98-2.05 (m, 2H), 1.55-1.65 (m, 2H).
Workup
- temperaturethe reaction was warmed to rt
- customThe reaction was quenched with sat'd aq NH4Cl
- additiondiluted with EtOAc
- washThe organic layer was washed with sat'd aq NH4Cl
- dry with materialdried over MgSO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe crude product was purified by silica gel chromatography (40 g silica gel, eluted with 0-100% EtOAc in hexanes)
Sources & evidence
- ORD record
- ord-9235252bd13d4361bbda9656b3466f96
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08791091B2
Reaction notes
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