Trifluoroacetic acid → HCID 46846899、化合物

反応式

[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]

参加物

反応物 2

HCID 6422Trifluoroacetic acid

HCID 67453605HCID 67453605、化合物

生成物 1

HCID 46846899HCID 46846899、化合物

実験手順

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).

後処理

concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード: ord-6749c070696b488195b722b4f0991fac
出典データセット: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
特許番号: US08354398B2

反応ノート

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