1,1-Dichloroethane → 1-(4-Fluoro-2-(trifluoromethyl)phenyl)piperazine

HRID 1868078Notes

Reaction equation

HRID 1868078 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[C:21]([F:24])([F:23])[F:22])[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.ClC(Cl)C>ClCCl>[F:20][C:17]1[CH:18]=[CH:19][C:14]([N:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)=[C:15]([C:21]([F:22])([F:24])[F:23])[CH:16]=1

Participants

5

Reactant 3

HCID 63651,1-DichloroethaneHCID 6422Trifluoroacetic acid2×HCID 57979766tert-Butyl 4-(4-fluoro-2-(trifluoromethyl)-phenyl)piperazine-1-carboxylate

Product 1

HCID 579797591-(4-Fluoro-2-(trifluoromethyl)phenyl)piperazineYield 79.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of tert-butyl-4-(4-fluoro-2-(trifluoromethyl)phenyl)piperazine-1-carboxylate (6.8 g, 19.5 mmol) in anhydrous dichloromethane (90 mL) was added TFA (45 mL) dropwise at 0° C. The reaction mixture was stirred at 0° C. for 15 minutes then the cooling bath was removed and it was allowed to stir at room temperature for 2 hours. Reaction was complete as determined by TLC. Most of TFA was azeotropped with dichloroethane. The residue was then diluted with dichloromethane and washed with saturated Na2CO3 (aq.). Organic layer was dried over MgSO4. Solvent evaporation afforded 1-(4-fluoro-2-(trifluoromethyl)phenyl)piperazine in 79.9% yield (3.86 g) as light brown oil. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 2.78-2.90 (m, 4H) 2.96-3.04 (m, 4H) 7.18-7.25 (m, 1H) 7.29-7.42 (m, 2H).

Workup

  1. customthe cooling bath was removed
  2. stirringto stir at room temperature for 2 hours
  3. customReaction
  4. washwashed with saturated Na2CO3 (aq.)
  5. dry with materialOrganic layer was dried over MgSO4
  6. customSolvent evaporation

Sources & evidence

ORD record
ord-45ebd62b611f43f69c2911b698043277
Source dataset
uspto-grants-2009_12
Patent number
US07632838B2

Reaction notes

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