Toluene → (s)-3-[5-Chloro-2-[1-(3-trifluoromethyl-phenyl)-ethoxy]-phenoxy]-azetidine

HRID 237259Notes

Reaction equation

HRID 237259 reaction equation
[C:1]([O:5]C([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=2[O:20][C@@H:21]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=2)[CH3:22])[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C1(C)C=CC=CC=1>C(Cl)Cl>[NH3:8].[CH3:1][OH:5].[Cl:19][C:17]1[CH:16]=[CH:15][C:14]([O:20][C@H:21]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:30])[F:31])[CH:24]=2)[CH3:22])=[C:13]([CH:18]=1)[O:12][CH:10]1[CH2:11][NH:8][CH2:9]1

Participants

6

Reactant 3

HCID 1140TolueneHCID 6422Trifluoroacetic acidHCID 67349743(R)-3-[5-Chloro-2-[1-(3-trifluoromethyl-phenyl)-ethoxy]-phenoxy]-azetidine-1-carboxylic acid tert-butyl ester

Product 2

HCID 21705897Ammonia methanolYield 1%HCID 46214155(s)-3-[5-Chloro-2-[1-(3-trifluoromethyl-phenyl)-ethoxy]-phenoxy]-azetidineYield 168.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

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).

Workup

  1. concentrationthe mixture concentrated
  2. extractionextracted with CH2Cl2 (2×)
  3. customThe combined organics were dried
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-092d6a1ef5a6452ea655749c7c5435c7
Source dataset
uspto-grants-2014_02
Patent number
US08642583B2

Reaction notes

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