Trifluoroacetic acid → 2,2,2-Trifluoro-1-[3-(2-methoxy-benzyl)-azetidin-1-yl]-ethanone

HRID 237299Notes

Reaction equation

HRID 237299 reaction equation
C([O:5][C:6]([N:8]1[CH2:11][CH:10]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19][CH3:20])[CH2:9]1)=O)(C)(C)C.C(O)([C:23]([F:26])([F:25])[F:24])=O.C(N(CC)CC)C.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl.CCOC(C)=O>[F:24][C:23]([F:26])([F:25])[C:6]([N:8]1[CH2:11][CH:10]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[O:19][CH3:20])[CH2:9]1)=[O:5]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 516892Sodium BicarbonateHCID 584051693-(2-Methoxy-benzyl)-azetidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 584050552,2,2-Trifluoro-1-[3-(2-methoxy-benzyl)-azetidin-1-yl]-ethanoneYield 75%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-(2-methoxy-benzyl)-azetidine-1-carboxylic acid tert-butyl ester (370 mg, 1.3 mmol) in DCM (10 mL) was added TFA (3 mL). After stirring for 16 h, TLC analysis indicated complete consumption of the starting material. To quench the reaction, saturated NaHCO3 solution and EtOAc were added. The aqueous portion was extracted twice with EtOAc and the combined organic extracts were dried (Na2SO4) and concentrated. To a solution of this material in DCM (20 mL) was added triethylamine (370 μL, 2.60 mmol) followed by trifluoroacetic anhydride (204 μL, 1.50 mmol). After 1 h, saturated NaHCO3 solution and EtOAc were added. The aqueous portion was extracted twice with EtOAc and the combined organic extracts were dried (Na2SO4) and concentrated to provide the title compound (274 mg, 75%). MS (ESI): mass calcd. for C13H14F3NO2, 273.1; m/z found, 274.2 [M+H]+. 1H NMR (CDCl3): 7.26-7.20 (m, 1H), 7.07 (dd, J=7.4, 1.6 Hz, 1H), 6.94-6.82 (m, 2H), 4.41 (dd, J=9.6, 8.4 Hz, 1H), 4.23-4.14 (m, 1H), 4.12-4.08 (m, 1H), 3.93-3.84 (m, 1H), 3.82 (s, 3H), 3.18-3.00 (m, 1H), 2.95-2.91 (m, 2H).

Workup

  1. customconsumption of the starting material
  2. customTo quench
  3. customthe reaction, saturated NaHCO3 solution and EtOAc
  4. additionwere added
  5. extractionThe aqueous portion was extracted twice with EtOAc
  6. dry with materialthe combined organic extracts were dried (Na2SO4)
  7. concentrationconcentrated
  8. waitAfter 1 h
  9. extractionThe aqueous portion was extracted twice with EtOAc
  10. dry with materialthe combined organic extracts were dried (Na2SO4)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-9b1f4ae216574d95ba92570024951d70
Source dataset
uspto-grants-2014_02
Patent number
US08642583B2

Reaction notes

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