Nitrogen → tert-Butyl 3,3-difluoro-4-(2-hydroxyethyl)piperidine-1-carboxylate
Reaction equation
N#N.C([O:5][C:6](=O)[CH2:7][CH:8]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][C:9]1([F:22])[F:21])C.CC(C[AlH]CC(C)C)C.[OH-].[Na+]>C1COCC1.O>[F:22][C:9]1([F:21])[CH:8]([CH2:7][CH2:6][OH:5])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:19])([CH3:18])[CH3:20])=[O:15])[CH2:10]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of tert-butyl 4-(2-ethoxy-2-oxoethyl)-3,3-difluoropiperidine-1-carboxylate (177 mg, 0.57 mmol) in dry THF (5.8 mL) was added DIBAL-H (1.0 M solution in THF, 1.15 mL, 1.15 mmol) at 0° C. The reaction mixture was stirred at rt for 2 h. The mixture was cooled down to 0° C., successively treated with H2O (0.23 mL) and 2N aq. NaOH (0.45 mL). The mixture was stirred at rt for 20 min, filtered through celite, washed with EA and the filtrate concentrated under reduced pressure. The crude residue was purified by FC (hept-EA, 1:1→1:2) and the title compound obtained as a colorless oil. LC-MS-conditions 08: tR=0.74 min; [M-CH3+H]+=251.34.
Workup
- temperatureThe mixture was cooled down to 0° C.
- stirringThe mixture was stirred at rt for 20 min
- filtrationfiltered through celite
- washwashed with EA
- concentrationthe filtrate concentrated under reduced pressure
- customThe crude residue was purified by FC (hept-EA, 1:1→1:2)
Sources & evidence
- ORD record
- ord-71299ff893e843beab2d0e6722a11f9a
- Source dataset
- uspto-grants-2015_11
- Patent number
- US09187435B2
Reaction notes
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