Water → 4-[5-(5-Chloro-6-isobutoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorobenzoic acid

HRID 219915ノート

反応式

HRID 219915 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:33]=[CH:32][C:27]([C:28]([O:30]C)=[O:29])=[C:26]([F:34])[CH:25]=3)[N:20]=2)[CH:15]=[N:16][C:17]=1Cl.[OH2:35]>CC(C)CO.C1COCC1.CCOC(C)=O>[Cl:11][C:12]1[CH:13]=[C:14]([C:19]2[O:23][N:22]=[C:21]([C:24]3[CH:33]=[CH:32][C:27]([C:28]([OH:30])=[O:29])=[C:26]([F:34])[CH:25]=3)[N:20]=2)[CH:15]=[N:16][C:17]=1[O:35][CH2:13][CH:14]([CH3:19])[CH3:15]

参加物

7

反応物 3

HCID 962WaterHCID 2733832Lithium HexamethyldisilazideHCID 86645653Methyl 4-[5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorobenzoate

生成物 1

HCID 252563804-[5-(5-Chloro-6-isobutoxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorobenzoic acid

試薬・触媒・溶媒 3

HCID 6560Isobutanol溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Lithium bis(trimethylsilyl)amide (700 μL; 1 M; 0.70 mmol) was added to a solution of methyl 4-[5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl]-2-fluorobenzoate, obtained in step 1 (73.63 mg; 0.20 mmol) in 2-methyl-1-propanol (3 mL) and THF (2 mL). The resulting mixture was stirred at RT for 1 h. Water (500 uL) was added and the mixture was stirred at RT for 3 h, saponification was complete. The reaction mixture was then diluted with EtOAc and washed with HCl 1N, NaCl sat. solution and dried over magnesium sulfate. After evaporation of the solvents, the crude was purified by HPLC prep to afford the title compound as a slightly yellow powder. 1H NMR (DMSO-d6, 300 MHz) δ 8.94 (d, J=2.2 Hz, 1H), 8.60 (d, J=2.2 Hz, 1H), 8.08 (t, J=7.7 Hz, 1H), 8.01 (dd, J=8.1, 1.5 Hz, 1H), 7.94 (dd, J=11.1, 1.5 Hz, 1H), 4.27 (d, J=6.5 Hz, 2H), 2.16-2.07 (m, 1H), 1.01 (d, J=6.6 Hz, 6H). LC/MS (Method B): 390.3 (M−H)−, 392.2 (M+H)+. HPLC (Method A) Rt 5.49 min (Purity: 98.6%).

後処理

  1. stirringthe mixture was stirred at RT for 3 h
  2. washwashed with HCl 1N, NaCl sat. solution
  3. dry with materialdried over magnesium sulfate
  4. customAfter evaporation of the solvents
  5. customthe crude was purified by HPLC prep

出典と根拠

ORDレコード
ord-7d264019e5964879a7ee08dc51b2d1fb
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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