Reaction #324441

Reaction equation

PhCH3

title compound

(R)-3-[5-Chloro-2-[1-(3-trifluoromethyl-phenyl)-ethoxy]-phenoxy]-azetidine-1-carboxylic acid tert-butyl ester

TFA

→

NH3 MeOH

Yield 1.0%

title compound

Yield 168.4%

(S)-3-[5-Chloro-2-[1-(3-trifluoromethyl-phenyl)-ethoxy]-phenoxy]-azetidine

Yield 168.4%

Solvents

CH2Cl2

CH2Cl2

Conditions

Workup

1. 1
   Concentrationthe mixture concentrated
2. 2
   Extractionextracted with CH2Cl2 (2×)
3. 3
   OtherThe combined organics were dried
4. 4
   Concentrationconcentrated

Procedure

To the title compound of Step A (5.1 g, 10.8 mmol) in CH2Cl2 (50 mL) at 0° C. was added TFA (50 mL). After 1 h, PhCH3 (50 mL) was added and the mixture concentrated. The resulting oil was neutralized with saturated NaHCO3 (aq.) and extracted with CH2Cl2 (2×). The combined organics were dried and concentrated. Silica gel chromatography (1-7% 2M NH3/MeOH in CH2Cl2) gave 3.38 g (83% yield) of the title compound as a clear oil. MS (ESI): mass calcd. for C18H17ClF3NO2, 371.1; m/z found, 372.0 [M+H]+. 1H NMR (CDCl3): 7.70 (s, 1H), 7.56-7.53 (m, 2H), 7.45 (t, J=7.7 Hz, 1H), 6.77 (dd, J=8.6, 2.3 Hz, 1H), 6.70 (d, J=8.6 Hz, 1H), 6.55 (d, J=2.4 Hz, 1H), 5.30 (q, J=6.3 Hz, 1H), 5.00-4.94 (m, 1H), 3.97-3.93 (m, 2H), 3.89-3.81 (m, 2H), 1.66 (d, J=6.5 Hz, 3H).

Source