Hydrochloric Acid → 1-[4-(Trifluoromethyl)phenyl]piperidin-4-ol
Reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.Br[C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=1.C1(P(C2CCCCC2)C2(C)CC=CC=C2C2C=CC=CC=2)CCCCC1.O1CCCC1.Cl.C(=O)([O-])O.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:16][C:15]([F:18])([F:17])[C:12]1[CH:13]=[CH:14][C:9]([N:5]2[CH2:6][CH2:7][CH:2]([OH:1])[CH2:3][CH2:4]2)=[CH:10][CH:11]=1Participants
Reactant 6
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 65 °C
Procedure
A mixture of 4-hydroxypiperidine (100 mg; 0.99 mmol), 4-bromo benzotrifluoride (0.167 mL, 1.19 mmol), tris(dibenzylideneacetone)dipalladium (37 mg; 0.04 mmol) and 2-(dicyclohexylphosphino)-2-methylbiphenyl (29 mg; 0.08 mmol) is thoroughly flushed with argon and tetrahydrofuran is added (1 mL). A molar solution of bis-(trimethylsilyl)-lithium amide in tetrahydrofuran (1.9 mL, 1.90 mmol) is added and the reaction mixture is heated at 65° C. After 17 hours reaction time, aq. 1M hydrochloric acid (7.5 mL) is added and the mixture is stirred for 15 minutes before neutralization by addition of aq. sat. sodium hydrogencarbonate. The mixture is extracted with ethyl acetate (2×10 mL). The combined organic layers are dried over sodium sulfate, filtered and evaporated under reduced pressure to yield crude 1-(4-trifluoromethyl-phenyl)-piperidin-4-ol.
Workup
- customis thoroughly flushed with argon and tetrahydrofuran
- additionis added (1 mL)
- additionis added
- extractionThe mixture is extracted with ethyl acetate (2×10 mL)
- dry with materialThe combined organic layers are dried over sodium sulfate
- filtrationfiltered
- customevaporated under reduced pressure
Sources & evidence
- ORD record
- ord-a623f685b8a24c1da5683b907081a0dd
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09096524B2
Reaction notes
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