Trifluoroacetic acid → 1-(4-(5-(5-(Pyridin-2-yl)-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid

HRID 1951939Notes

Reaction equation

HRID 1951939 reaction equation
C([O:5][C:6]([CH:8]1[CH2:11][N:10]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]3[N:23]=[C:22]([C:24]4[C:28]([C:29]([F:32])([F:31])[F:30])=[C:27]([C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=5)[O:26][N:25]=4)[O:21][N:20]=3)=[CH:15][CH:14]=2)[CH2:9]1)=[O:7])(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[N:34]1[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=1[C:27]1[O:26][N:25]=[C:24]([C:22]2[O:21][N:20]=[C:19]([C:16]3[CH:17]=[CH:18][C:13]([CH2:12][N:10]4[CH2:11][CH:8]([C:6]([OH:7])=[O:5])[CH2:9]4)=[CH:14][CH:15]=3)[N:23]=2)[C:28]=1[C:29]([F:31])([F:30])[F:32]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66678445Tert-butyl-1-(4-(5-(5-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate

Product 1

HCID 468471441-(4-(5-(5-(Pyridin-2-yl)-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl-1-(4-(5-(5-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (previous reaction) in dichloromethane (0.5 mL) was added trifluoroacetic acid (0.5 mL), and the mixture was stirred at room temperature for 30 min. The reaction mixture was concentrated under reduced pressure, and the residue was treated with triethylamine and re-concentrated. The product mixture was purified by flash silica gel chromatography using a mixture of methanol, dichloromethane, and ammonium hydroxide (10:90:0-10:90:1-15:85:1-20:80:1) to give 1-(4-(5-(5-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid (0.007 g, 0.015 mmol) as an off-white solid. The product had an HPLC retention time=2.33 min.—Column: CHROMOLITH® SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=472.0. 1H NMR (500 MHz, methanol-d3) δ ppm 3.50 (quin, J=8.25 Hz, 1H), 4.21-4.29 (m, 4H), 4.46 (s, 2H), 7.66-7.71 (m, 3H), 8.02-8.05 (m, 1H), 8.08-8.13 (m, 1H), 8.28 (d, J=8.25 Hz, 2H), and 8.83-8.85 (m, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionthe residue was treated with triethylamine
  3. concentrationre-concentrated
  4. customThe product mixture was purified by flash silica gel chromatography
  5. additiona mixture of methanol, dichloromethane, and ammonium hydroxide (10:90:0-10:90:1-15:85:1-20:80:1)

Sources & evidence

ORD record
ord-43092f2ca3234d7d991593699024b864
Source dataset
uspto-grants-2013_03
Patent number
US08404672B2

Reaction notes

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