Trifluoroacetic acid → 4-(4-(Azetidin-3-yloxy)-2-methoxybenzyl)morpholine

HRID 1035171Notes

Reaction equation

HRID 1035171 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:18]=[CH:19][C:20]=1[CH2:21][N:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1)[O:6][CH:7]1[CH2:10][N:9](C(OC(C)(C)C)=O)[CH2:8]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:9]1[CH2:10][CH:7]([O:6][C:5]2[CH:18]=[CH:19][C:20]([CH2:21][N:22]3[CH2:23][CH2:24][O:25][CH2:26][CH2:27]3)=[C:3]([O:2][CH3:1])[CH:4]=2)[CH2:8]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58043136HCID 58043136, compound

Product 1

HCID 670166284-(4-(Azetidin-3-yloxy)-2-methoxybenzyl)morpholineYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 7B (2.1 g, 5.47 mmol) in DCM (20 mL) was treated with TFA (10 g, 88 mmol) and stirred at RT for 2 h. The reaction mixture was concentrated and the residue was dissolved in aqueous NaHCO3 (sat.) and extracted several times with DCM and 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 1.0 g (66%) of 7C as a colorless oil. 1H NMR (500 MHz, CDCl3): δ 2.40-2.53 (m, 4H), 3.47 (s, 2H), 3.66-3.74 (m, 4H), 3.78 (s, 3H), 3.77-3.84 (m, 2H), 3.89-3.97 (m, 2H), 4.94-5.04 (m, 1H), 6.23 (d, 1H), 6.37 (s, 1H), 7.19 (d, 1H).

Workup

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

Sources & evidence

ORD record
ord-dc1bfb59ebf94e118e195ed8c0a158b8
Source dataset
uspto-grants-2013_10
Patent number
US08546375B2

Reaction notes

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