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

HRID 1035175Notes

Reaction equation

[CH3:1][C:2]1[CH:19]=[C:18]([CH2:20][N:21]2[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]2)[CH:17]=[CH:16][C:3]=1[O:4][CH:5]1[CH2:8][N:7](C(OC(C)(C)C)=O)[CH2:6]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:7]1[CH2:6][CH:5]([O:4][C:3]2[CH:16]=[CH:17][C:18]([CH2:20][N:21]3[CH2:22][CH2:23][N:24]([CH3:27])[CH2:25][CH2:26]3)=[CH:19][C:2]=2[CH3:1])[CH2:8]1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 9B (2.18 g, 5.81 mmol) in DCM (40 mL) was treated with TFA (10 g, 88 mmol) and stirred at 0° C. for 3 h. The reaction mixture was concentrated and the residue was dissolved in aqueous NaHCO3 (sat.) and extracted several times with DCM. The organic solutions were filtered through a phase separator. The solvent was removed by evaporation and the residue was purified by column chromatography on SiO2 using 10% triethylamine and 10% MeOH in EtOAc as eluent. There was obtained 1.44 g (90%) of 9C as a colorless oil. 1H NMR (500 MHz, CDCl3): δ 2.22 (s, 3H), 2.28 (s, 3H), 2.27-2.70 (bm, 8H), 3.40 (s, 2H), 3.75-3.85 (m, 2H), 3.88-3.98 (m, 2H), 4.92-5.02 (m, 1H), 6.43 (d, 1H), 7.01 (d, 1H), 7.09 (s, 1H).

Workup

concentrationThe reaction mixture was concentrated
dissolutionthe residue was dissolved in aqueous NaHCO3 (sat.)
extractionextracted several times with DCM
filtrationThe organic solutions were filtered through a phase separator
customThe solvent was removed by evaporation
customthe residue was purified by column chromatography on SiO2 using 10% triethylamine and 10% MeOH in EtOAc as eluent

Sources & evidence

ORD record: ord-0c03900dfaae403aa085f24014b052d0
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546375B2

Reaction notes

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