Hydrochloric Acid → 3-[[4-Methoxy-2′-(trifluoromethyl)[1,1′-biphenyl]-3-yl]oxy]azetidine

HRID 1850080Notes

Reaction equation

HRID 1850080 reaction equation
[C:1]([O:5]C([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:14]=[C:15]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[C:27]([F:30])([F:29])[F:28])[CH:16]=[CH:17][C:18]=2[O:19][CH3:20])[CH2:9]1)=O)(C)(C)C.Cl.C([O-])(O)=O.[Na+]>CCOC(C)=O.O1CCOCC1>[NH3:8].[CH3:1][OH:5].[CH3:20][O:19][C:18]1[CH:17]=[CH:16][C:15]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[C:27]([F:30])([F:29])[F:28])=[CH:14][C:13]=1[O:12][CH:10]1[CH2:9][NH:8][CH2:11]1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 67342335HCID 67342335, compound

Product 2

HCID 21705897Ammonia methanolYield 10%HCID 461964483-[[4-Methoxy-2′-(trifluoromethyl)[1,1′-biphenyl]-3-yl]oxy]azetidineYield 122.9%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To title compound of Step E (0.062 g, 0.146 mmol) in EtOAc (2 mL) was added 4M HCl in dioxane (2 mL). After 18 h, the reaction was neutralized with saturated NaHCO3 (aq.) and extracted with CH2Cl2 (2×). The combined organics were dried and concentrated. Silica gel chromatography (10-80% 2M NH3/MeOH in CH2Cl2) gave 0.029 g (61%) of the title compound. MS (ESI): mass calcd. for C17H16F3NO2, 323.11. m/z found, 324.2 [M+H]+. 1H NMR (CDCl3): 7.73 (d, J=7.8 Hz, 1H), 7.54 (t, J=7.3 Hz, 1H), 7.45 (t, J=7.6 Hz, 1H), 7.32 (d, J=7.6 Hz, 1H), 6.90 (td, J=8.2, 5.1 Hz, 2H), 6.59 (s, 1H), 5.02-4.97 (m, 1H), 3.92 (s, 3H), 3.96-3.85 (m, 7H).

Workup

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

Sources & evidence

ORD record
ord-8bf33b46c60b463084aa58ee5a6f091d
Source dataset
uspto-grants-2015_02
Patent number
US08957059B2

Reaction notes

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