N,N-Diethylethanamine trihydrofluoride → HCID 86732159, compound
Reaction equation
[B-](F)(F)(F)F.CCN([S+](F)F)CC.[CH:14]([CH:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[CH2:18][CH2:17]1)=O.[FH:32].[FH:33].F.C(N(CC)CC)C>ClCCl>[F:32][CH:14]([F:33])[CH:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[CH2:18][CH2:17]1Participants
Procedure
To a cooled (0° C.) solution of XtalFluor-E (4.50 g, 19.65 mmol) in dichloromethane (50 mL) was added a solution of 4-formyl-N-CBZ-piperidine (2.30 g, 9.30 mmol, Oakwood) in dichloromethane (7 mL) followed by triethylamine trihydrofluoride (3.00 mL, 18.40 mmol). The reaction was allowed to warm to room temperature overnight. Then the reaction mixture was cooled to 0° C. and quenched slowly with saturated NaHCO3 solution. The layers were separated and the aqueous layer was extracted with dichloromethane (3×). The combined organic layers were evaporated onto silica gel and purified by flash chromatography (Isco 40 g) eluting with (EtOAc):hexanes (0:1→1:1) to give benzyl 4-(difluoromethyl)piperidine-1-carboxylate as a light-yellow oil (1.16 g, 46% yield).
Workup
- temperatureThen the reaction mixture was cooled to 0° C.
- customquenched slowly with saturated NaHCO3 solution
- customThe layers were separated
- extractionthe aqueous layer was extracted with dichloromethane (3×)
- customThe combined organic layers were evaporated onto silica gel
- custompurified by flash chromatography (Isco 40 g)
- washeluting with (EtOAc)
Sources & evidence
- ORD record
- ord-4ef457703be64b36afaa5837f5e69feb
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09296734B2
Reaction notes
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