Lithium Hexamethyldisilazide → {4-[5-(5-Chloro-6-isobutoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorophenoxy}acetic acid

HRID 219932ノート

反応式

HRID 219932 の反応式
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:11][C:12]1[CH:13]=[C:14]([C:19]2[O:23][N:22]=[C:21]([C:24]3[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([O:32]C(C)(C)C)=[O:31])=[C:26]([F:39])[CH:25]=3)[N:20]=2)[CH:15]=[N:16][C:17]=1Cl>CC(C)CO.C1COCC1>[Cl:11][C:12]1[CH:13]=[C:14]([C:19]2[O:23][N:22]=[C:21]([C:24]3[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([OH:32])=[O:31])=[C:26]([F:39])[CH:25]=3)[N:20]=2)[CH:15]=[N:16][C:17]=1[O:23][CH2:19][CH:14]([CH3:15])[CH3:13]

参加物

5

反応物 2

HCID 2733832Lithium HexamethyldisilazideHCID 86645655Tert-butyl {4-[5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorophenoxy}acetate

生成物 1

HCID 59495678{4-[5-(5-Chloro-6-isobutoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorophenoxy}acetic acid

試薬・触媒・溶媒 2

HCID 6560Isobutanol溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
130 °C

実験手順

Lithium bis(trimethylsilyl)amide (225 μl; 1 M; 0.22 mmol) was added to a solution of tert-butyl {4-[5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorophenoxy}acetate (66.04 mg; 0.15 mmol) in 2-methyl-1-propanol (1.50 mL) and THF (2 mL). The resulting mixture was heated at 130° C. for 10 min in the microwave. A mixture of the desired product and the isopropyl ester was isolated. NaOH (5N solution; 5 eq; 0.15 mL) was added and the mixture was stirred at RT for 2 hours. The reaction mixture was diluted with EtOAc and washed with HCl 1N, brine and dried over MgSO4. After evaporation of the solvents, the title product was isolated as white solid (51 mg; 81%). 1H NMR (DMSO-d6, 300 MHz) δ 13.25 (br s, 1H), 8.91 (d, J=2 Hz, 1H), 8.57 (d, J=2 Hz, 1H), 7.90-7.86 (m, 2H), 7.32 (t, J=9 Hz, 1H), 4.91 (s, 2H), 4.27 (d, J=6 Hz, 2H), 2.12 (m, 1H), 1.02 (d, J=6 Hz, 6H). LC/MS (Method B): 420.3 (M−H)−. HPLC (Method A) Rt 5.29 min (Purity: 100%).

出典と根拠

ORDレコード
ord-1fb00fc435ea49e39aba0a9b884ab9a2
出典データセット
uspto-grants-2012_06
特許番号
US08202865B2

反応ノート

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