Trifluoroacetic acid → 1-(4-(Azetidin-3-yloxy)benzyl)pyrrolidine

HRID 1035165Notes

Reaction equation

HRID 1035165 reaction equation
[N:1]1([CH2:6][C:7]2[CH:24]=[CH:23][C:10]([O:11][CH:12]3[CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13]3)=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:14]1[CH2:13][CH:12]([O:11][C:10]2[CH:23]=[CH:24][C:7]([CH2:6][N:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)=[CH:8][CH:9]=2)[CH2:15]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58043117Tert-butyl 3-(4-(pyrrolidin-1-ylmethyl)phenoxy)azetidine-1-carboxylate

Product 1

HCID 670165201-(4-(Azetidin-3-yloxy)benzyl)pyrrolidineYield 86.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1A (5.2 g, 15.5 mmol) in DCM (50 mL) was treated with TFA (10 g, 88 mmol) and stirred at RT for 17 h. The reaction mixture was concentrated and then co-evaporated using DCM. The residue was dissolved in water and the pH adjusted to pH 10 by adding NaOH. The solution was extracted several times with DCM and the organic solutions were filtered through a phase separator. The solvent was removed by evaporation. There was obtained 3.1 g (85%) of 1B as an oil. 1H NMR (500 MHz, CDCl3): δ 1.69-1.83 (m, 4H), 2.43-2.57 (m, 4H), 3.53 (s, 2H), 3.73-3.81 (m, 2H), 3.87-3.92 (m, 2H), 4.93-5.01 (m, 1H), 6.68 (d, 2H), 7.20 (d, 2H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionThe residue was dissolved in water
  3. additionby adding NaOH
  4. extractionThe solution was extracted several times with DCM
  5. filtrationthe organic solutions were filtered through a phase separator
  6. customThe solvent was removed by evaporation

Sources & evidence

ORD record
ord-4420dbdacbd1460d837bd5aa37816600
Source dataset
uspto-grants-2013_10
Patent number
US08546375B2

Reaction notes

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