1-Chloro-4-(trifluoromethyl)benzene → 1-[4-(Trifluoromethyl)phenyl]piperidine

HRID 1955320

Reaction equation

HRID 1955320 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.[NH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.CC([O-])(C)C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:12]1([C:2]2[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=2)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1

Participants

6

Reactant 3

HCID 73941-Chloro-4-(trifluoromethyl)benzeneHCID 8082PiperidineHCID 23676156Sodium t-butoxide

Product 1

HCID 4250921-[4-(Trifluoromethyl)phenyl]piperidineYield 23.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

The general procedure from Example 1 was followed using 4-chlorobenzo-trifluoride (650 mg, 3.6 mmol) and piperidine (258 mg, 3.0 mmol) with Pd2 (dba)3 (55 mg, 0.081 mmol) and (Me3C)2PH(O) (21.0 mg, 0.126 mmol) and NaOtBu (432 mg, 4.5 mmol) in 6.0 mL of toluene. After 48 h, the reaction mixture was chromatographed with 5% ethyl acetate/hexane to give 161 mg (23% yield) of 4-piperidinobenzotrifluoride. It was >95% pure by 1H NMR and GC/MS. 1H NMR (500 MHz, CDCl3): δ 7.36 (d, J=8.78 Hz, 2H), 6.82 (d, J=8.79 Hz, 2H), 3.18 (m, 4H), 1.60 (m, 4H), 1.54 (m, 2H) ppm. 13C NMR (125 MHz, CDCl3): d 153.7, 127.6, 126.3, 114.5, 49.2, 25.4, 24.2 ppm. MS: Calculated for C12H14F3N(M+): 229.1. Found: 230.2 (M+ +H).

Workup

  1. customthe reaction mixture was chromatographed with 5% ethyl acetate/hexane

Sources & evidence

ORD record
ord-489a71a85ad34762bab1fe194a7657cb
Source dataset
uspto-grants-2000_09
Patent number
US06124462

Linked notes

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