Trifluoroacetic acid → HCID 46846900, compound

HRID 1804458Notes

Reaction equation

[CH2:1]([C:5]1[C:6]([C:16]2[O:20][N:19]=[C:18]([C:21]3[CH:38]=[CH:37][C:24]([CH2:25][N:26]4[CH2:29][CH:28]([C:30]([O:32]C(C)(C)C)=[O:31])[CH2:27]4)=[CH:23][CH:22]=3)[N:17]=2)=[N:7][O:8][C:9]=1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH:2]([CH3:4])[CH3:3].FC(F)(F)C(O)=O>>[CH2:1]([C:5]1[C:6]([C:16]2[O:20][N:19]=[C:18]([C:21]3[CH:22]=[CH:23][C:24]([CH2:25][N:26]4[CH2:27][CH:28]([C:30]([OH:32])=[O:31])[CH2:29]4)=[CH:37][CH:38]=3)[N:17]=2)=[N:7][O:8][C:9]=1[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[CH:2]([CH3:4])[CH3:3]

Participants

Reactant 2

HCID 6422Trifluoroacetic acid

HCID 67456933Tert-butyl 1-(4-(5-(4-isobutyl-5-phenylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate

Product 1

HCID 46846900HCID 46846900, compound

Procedure

The tert-butyl 1-(4-(5-(4-isobutyl-5-phenylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)-azetidine-3-carboxylate intermediate was stirred in trifluoroacetic acid (3.64 mL, 47.2 mmol) for 30 min. and concentrated under reduced pressure to give the desired product as a pale yellow solid. The solid was dispersed in water with some methanol with sonication. The pH was adjusted to ˜4, and the resulting solid was collected by vacuum filtration, washed with water (3×), and dried. The white solid was triturated with methanol with sonication and filtered to give 1-(4-(5-(4-isobutyl-5-phenylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid (0.074 g, 0.161 mmol, 34.2% yield) as a white, crystalline solid. The compound had an HPLC ret. time=2.99 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=459.3. 1H NMR (500 MHz, DMSO-d6) δ ppm 0.87 (d, J=6.60 Hz, 6H), 1.93 (ddd, J=13.61, 6.74, 6.60 Hz, 1H), 2.99 (d, J=7.15 Hz, 2H), 3.24 (br. s., 3H), 3.43 (s, 2H), 3.66 (s, 2H), 7.53 (d, J=7.70 Hz, 2H), 7.58-7.67 (m, 3H), 7.87 (d, J=6.60 Hz, 2H), and 8.06 (d, 2H). The methanol filtrate was concentrated under reduce pressure to give additional 1-(4-(5-(4-isobutyl-5-phenylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid (0.034 g, 0.066 mmol, 13.99% yield) as a pale yellow solid (HPLC purity=89%).

Workup

concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-fe9be56bdab54f0da9071957ae2fed9e
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354398B2

Reaction notes

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