Tetrahydrofuran → 2-(3-hydroxy-4-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)butylcarbamoyl)benzoic acid

HRID 474281

Reaction equation

HRID 474281 reaction equation
[H-].[Na+].[OH:3][CH:4]([CH2:18][OH:19])[CH2:5][CH2:6][N:7]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]1=[O:17].F[C:21]1[CH:26]=[C:25]([N+:27]([O-:29])=[O:28])[CH:24]=[CH:23][C:22]=1[N:30]1[CH:34]=[N:33][C:32]([CH3:35])=[N:31]1.C1C[O:39]CC1>>[OH:3][CH:4]([CH2:18][O:19][C:21]1[CH:26]=[C:25]([N+:27]([O-:29])=[O:28])[CH:24]=[CH:23][C:22]=1[N:30]1[CH:34]=[N:33][C:32]([CH3:35])=[N:31]1)[CH2:5][CH2:6][NH:7][C:15]([C:14]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:8]([OH:39])=[O:17])=[O:16]

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran3×HCID 24758Sodium hydrideHCID 215924892-(3,4-Dihydroxybutyl)isoindoline-1,3-dioneHCID 575269631-(2-fluoro-4-nitrophenyl)-3-methyl-1H-1,2,4-triazole

Product 1

HCID 666683182-(3-hydroxy-4-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)butylcarbamoyl)benzoic acid

Conditions

Temperature
0 °C

Procedure

Sodium hydride (0.827 g, 20.67 mmol) was suspended in THF (10 mL), and then 2-(3,4-dihydroxybutyl)isoindoline-1,3-dione (3.24 g, 13.78 mmol) in THF (20.0 mL) was added. This reaction mixture was stirred at 0° C. for 10 min, followed by the addition of 1-(2-fluoro-4-nitrophenyl)-3-methyl-1H-1,2,4-triazole (2.041 g, 9.19 mmol) in THF (16.0 mL). The mixture was stirred at 0° C. for 1 h and then stirred for an additional 2 h at rt. The reaction was quenched with water and washed with EtOAc. The aqueous layer was acidified to pH 2˜4 and then extracted with EtOAc. The combined EtOAc layers were concentrated in vacuo to get 2-(3-hydroxy-4-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)butylcarbamoyl)benzoic acid, which is used as-is in the next step. LC-MS (M+H)+=456.1. 1H NMR (500 MHz, methanol-d4) δ 9.31 (s, 1H), 8.15-8.01 (m, 3H), 7.86-7.76 (m, 2H), 7.51-7.46 (m, 2H), 4.43-4.42 (m, 1H), 4.29-4.27 (m, 1H), 3.91-3.87 (m, 1H), 3.63-3.47 (m, 2H), 2.47 (s, 3H), 2.05-1.98 (m, 1H), 1.87-1.84 (m, 1H).

Workup

  1. stirringThe mixture was stirred at 0° C. for 1 h
  2. stirringstirred for an additional 2 h at rt
  3. customThe reaction was quenched with water
  4. washwashed with EtOAc
  5. extractionextracted with EtOAc
  6. concentrationThe combined EtOAc layers were concentrated in vacuo

Sources & evidence

ORD record
ord-fc60c40595de4c53a7c5ada5f11c2661
Source dataset
uspto-grants-2014_01
Patent number
US08637523B2

Linked notes

Loading…