Tert-butyl 1-(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate → 1-(4-(5-(4-Phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid

HRID 1951957Notes

Reaction equation

HRID 1951957 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:38]=[CH:37][C:24]([CH2:25][N:26]5[CH2:29][CH:28]([C:30]([O:32]C(C)(C)C)=[O:31])[CH2:27]5)=[CH:23][CH:22]=4)[N:17]=3)[S:10][C:11]=2[C:12]([F:15])([F:14])[F:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>FC(F)(F)C(O)=O.CO>[C:1]1([C:7]2[CH:8]=[C:9]([C:16]3[O:20][N:19]=[C:18]([C:21]4[CH:38]=[CH:37][C:24]([CH2:25][N:26]5[CH2:27][CH:28]([C:30]([OH:32])=[O:31])[CH2:29]5)=[CH:23][CH:22]=4)[N:17]=3)[S:10][C:11]=2[C:12]([F:13])([F:15])[F:14])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 1

HCID 66678166Tert-butyl 1-(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate

Product 1

HCID 101742551-(4-(5-(4-Phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acidYield 74%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of tert-butyl 1-(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (518 mg, 0.956 mmol) in trifluoroacetic acid (15 mL) was allowed to stand at room temperature for 1.5 h. The volatiles were removed under reduced pressure, and the residue was co-evaporated from ethyl acetate/hexanes. (2×10 mL). The residue was suspended in water (10 mL) and the pH was adjusted to ˜11 with 1N aqueous sodium hydroxide. To this solution was added sufficient 1N aqueous hydrochloric acid to adjust the pH ˜4.5. The resulting suspension was stirred at room temperature overnight. The white suspension was filtered through a medium porosity sintered glass filter, and the filter cake was washed thoroughly with water. The solid was dried, the white powder was suspended in methanol, and the suspension was sonicated until it was uniform. The methanol was removed under reduced pressure, and the procedure was repeated twice more to afford a white solid that was stirred as a suspension in methanol (˜30 mL) overnight. Vacuum filtration and drying afforded 1-(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxadiazol-3-yl)benzyl)-azetidine-3-carboxylic acid (345 mg, 0.707 mmol, 74% yield) as a white powder. HPLC ret. time=3.45 min. (YMC Combi S-5 4.6×50 mm ODS column) eluting with 10-90% aqueous methanol+0.2% phosphoric acid over a 4 minute gradient. MS: (M+H)=486.12. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.23 (s, 3H), 3.39-3.45 (m, 2H), 3.64 (s, 2H), 7.50 (d, J=8.28 Hz, 2H), 7.58 (m, 5H), 8.02 (d, J=8.28 Hz, 2H), and 8.26 (d, J=1.25 Hz, 1H). Elemental Analysis: Calc. for C24H18N3O3SF3.0.1H2O: C, 59.22; H, 3.76; N, 8.63; S, 6.59; F, 11.71. Found: C24H18N3O3SF3.0.1H2O: C, 59.06; H, 3.45; N, 8.60; S, 6.61; F, 11.42; KF (Found)=0.25% water.

Workup

  1. customThe volatiles were removed under reduced pressure
  2. additionTo this solution was added sufficient 1N aqueous hydrochloric acid
  3. filtrationThe white suspension was filtered through a medium porosity sintered glass
  4. filtrationfilter
  5. washthe filter cake was washed thoroughly with water
  6. customThe solid was dried
  7. customthe suspension was sonicated until it
  8. customThe methanol was removed under reduced pressure
  9. customto afford a white solid
  10. filtrationVacuum filtration
  11. customdrying

Sources & evidence

ORD record
ord-9b74f10120424dcabc26ef1a492bb41d
Source dataset
uspto-grants-2013_03
Patent number
US08404672B2

Reaction notes

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