Trifluoroacetic acid → 1-(4-(Azetidin-3-yloxy)-2-fluorobenzyl)-4-methylpiperazine

HRID 1035196Notes

Reaction equation

HRID 1035196 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[CH2:20][N:21]1[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]1)[O:5][CH:6]1[CH2:9][N:8](C(OC(C)(C)C)=O)[CH2:7]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:8]1[CH2:9][CH:6]([O:5][C:4]2[CH:17]=[CH:18][C:19]([CH2:20][N:21]3[CH2:22][CH2:23][N:24]([CH3:27])[CH2:25][CH2:26]3)=[C:2]([F:1])[CH:3]=2)[CH2:7]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58043154tert-Butyl 3-(3-fluoro-4-((4-methylpiperazin-1-yl)methyl)phenoxy)azetidine-1-carboxylate

Product 1

HCID 666534801-(4-(Azetidin-3-yloxy)-2-fluorobenzyl)-4-methylpiperazineYield 32%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 29C (0.9 g, 2.4 mmol) in DCM (20 mL) was treated with TFA (10 g, 88 mmol) and stirred at 0° C. for 4 h. The reaction mixture was concentrated and the residue was dissolved in aqueous NaHCO3 (sat.). The mixture was extracted three times with DCM and the organic solutions were filtered through a phase separator. The solvent was removed by evaporation. There was obtained 0.21 g (32%) of 29D as a colorless oil. 1H NMR (500 MHz, CDCl3): δ 2.28 (s, 3H), 2.28-2.68 (bm, 8H), 3.52 (s, 2H), 3.69-3.85 (m, 2H), 3.85-4.02 (m, 2H), 4.88-5.03 (m, 1H), 6.36-6.58 (m, 2H), 7.15-7.27 (m, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in aqueous NaHCO3 (sat.)
  3. extractionThe mixture was extracted three times with DCM
  4. filtrationthe organic solutions were filtered through a phase separator
  5. customThe solvent was removed by evaporation

Sources & evidence

ORD record
ord-b637d2ba530f4ba58e53b53bfa8073e8
Source dataset
uspto-grants-2013_10
Patent number
US08546375B2

Reaction notes

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