Ethyl 4-piperidinecarboxylate → Ethyl 1-(2,2,2-trifluoro-1-(3-(trifluoromethyl)phenyl)ethyl)piperidine-4-carboxylate

HRID 1897965Notes

Reaction equation

HRID 1897965 reaction equation
[F:1][C:2]([F:16])([F:15])[C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]([F:14])([F:13])[F:12])[CH:6]=1)=O.[NH:17]1[CH2:27][CH2:26][CH:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:19][CH2:18]1.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>ClCCl.CO.[Ti](Cl)(Cl)(Cl)Cl.C(OCC)(=O)C.C1(C)C=CC=CC=1.C(N(CC)CC)C>[F:1][C:2]([F:16])([F:15])[CH:3]([N:17]1[CH2:27][CH2:26][CH:20]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:19][CH2:18]1)[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]([F:14])([F:13])[F:12])[CH:6]=1

Participants

11

Reactant 4

HCID 70770Ethyl 4-piperidinecarboxylateHCID 1365592,2,2-Trifluoro-3'-(trifluoromethyl)acetophenoneHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 86649627Ethyl 1-(2,2,2-trifluoro-1-(3-(trifluoromethyl)phenyl)ethyl)piperidine-4-carboxylate

Reagents, catalysts & solvents 6

HCID 24193Titanium TetrachlorideCatalystHCID 887MethanolSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 0.355 ml of 2,2,2-trifluoro-1-(3-(trifluoromethyl)phenyl)ethanone in 12 ml of dichloromethane were added 0.32 ml of ethyl isonipecotate, 0.58 ml of triethylamine and 1.05 ml of a toluene solution containing 1 M titanium(IV) chloride at room temperature, followed by stirring the reaction mixture at room temperature overnight. To the reaction mixture was added a solution of 392 mg of sodium cyanoborohydride in 5 ml of methanol at room temperature, followed by stirring the reaction mixture at room temperature for 6 hours. Ethyl acetate and saturated aqueous sodium bicarbonate solution were added to the reaction mixture. An insoluble matter was filtered off using Celite. The ethyl acetate layer was separated, washed with brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated in vacuo. The resulting residue was purified by a silica gel column chromatography (eluent: hexane to hexane/ethyl acetate=4/1) to give the title compound as a yellow oil.

Workup

  1. stirringby stirring the reaction mixture at room temperature for 6 hours
  2. filtrationAn insoluble matter was filtered off
  3. customThe ethyl acetate layer was separated
  4. washwashed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customThe resulting residue was purified by a silica gel column chromatography (eluent: hexane to hexane/ethyl acetate=4/1)

Sources & evidence

ORD record
ord-0d332d6174b84c70b4e2fbdbd85b866a
Source dataset
uspto-grants-2013_08
Patent number
US08519136B2

Reaction notes

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