Trifluoroacetic acid → HCID 46846899, Verbindung

HRID 1804455Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1804455
[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)[CH2:2][CH2:3][CH3:4].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)[CH2:2][CH2:3][CH3:4]

Komponenten

3

Edukt 2

HCID 6422Trifluoroacetic acidHCID 67453605HCID 67453605, Verbindung

Produkt 1

HCID 46846899HCID 46846899, Verbindung

Versuchsvorschrift

The tert-butyl 1-(4-(5-(4-butyl-5-phenylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)-azetidine-3-carboxylate intermediate (0.156 g) was stirred in trifluoroacetic acid (4.03 mL, 52.3 mmol) for 30 min. and concentrated under reduced pressure to give the desired product as a yellow, viscous oil. The oil was dissolved in dichloromethane and washed with a saturated aqueous solution of sodium bicarbonate. The organic layer, which contained the product (presumably as the sodium salt) was concentrated under reduced pressure. The white, solid residue was dissolved in water (pH ˜9), and the pH was adjusted to ˜4.5 with concentrated hydrochloric acid. The resulting white precipitate was collected by vacuum filtration and dried (no additional product in aqueous layer by HPLC). The solid was diluted with methanol and sonicated for 5 min. The methanol was removed under reduced pressure. The resulting solid was once again diluted with methanol, sonicated, collected by vacuum filtration, and washed with methanol. The resulting solid was dried well to give 1-(4-(5-(4-butyl-5-phenylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid (0.102 g, 0.222 mmol, 42.5% yield) as a white, crystalline solid (There was some product remaining in the methanol filtrate). The compound had an HPLC with a ret. time=3.11 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=459.1. 1H NMR (500 MHz, DMSO-d6) δ ppm 0.91 (t, J=7.42 Hz, 3H), 1.37-1.46 (m, 2H), 1.62-1.70 (m, 2H), 3.00-3.06 (m, 2H), 3.23 (br. s., 3H), 3.43 (br. s., 2H), 3.65 (s, 2H), 7.52 (d, J=8.25 Hz, 2H), 7.59-7.68 (m, 3H), 7.83 (d, J=7.15 Hz, 2H), 8.06 (d, J=8.25 Hz, 2H), and 12.27 (s, 1H).

Aufarbeitung

  1. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-6749c070696b488195b722b4f0991fac
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08354398B2

Notizen zur Reaktion

Wird geladen…