Sodium hydride → tert-butyl (4-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)butyl)carbamate

HRID 474278

Reaction equation

HRID 474278 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:15])[NH:9][CH2:10][CH2:11][CH2:12][CH2:13][OH:14])([CH3:6])([CH3:5])[CH3:4].F[C:17]1[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[CH:20]=[CH:19][C:18]=1[N:26]1[CH:30]=[N:29][C:28]([CH3:31])=[N:27]1>C1COCC1>[CH3:31][C:28]1[N:29]=[CH:30][N:26]([C:18]2[CH:17]=[CH:22][C:21]([N+:23]([O-:25])=[O:24])=[CH:20][C:19]=2[O:14][CH2:13][CH2:12][CH2:11][CH2:10][NH:9][C:8](=[O:15])[O:7][C:3]([CH3:6])([CH3:4])[CH3:5])[N:27]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 545141tert-Butyl N-(4-hydroxybutyl)carbamateHCID 575269631-(2-fluoro-4-nitrophenyl)-3-methyl-1H-1,2,4-triazole

Product 1

HCID 66666004tert-butyl (4-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)butyl)carbamateYield 99.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

Sodium hydride (0.405 g, 10.13 mmol) was suspended in THF (6 mL), and then tert-butyl-(4-hydroxybutyl)carbamate (1.278 g, 6.75 mmol) in THF (6.0 mL) was added. The 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 (1.0 g, 4.50 mmol) in THF (10.0 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 extracted with EtOAc three times. After concentrating the combined EtOAc layers, the residue was purified by flash chromatography (silica gel, 300 g, 0 to 80% EtOAc/Hexane) to get tert-butyl (4-(2-(3-methyl-1H-1,2,4-triazol-1-yl)-5-nitrophenoxy)butyl)carbamate (1.75 g, 99% yield). LC-MS (M+Na)+=414.5. 1H NMR (500 MHz, chloroform-d) δ 8.88 (s, 1H), 8.10 (d, J=8.8 Hz, 1H), 8.00 (dd, J=8.9, 2.3 Hz, 1H), 7.95 (d, J=2.3 Hz, 1H), 4.28 (t, J=6.5 Hz, 2H), 3.22 (d, J=6.4 Hz, 2H), 2.52 (s, 3H), 2.01-1.92 (m, 2H), 1.74-1.68 (m, 2H), 1.46 (s, 9H).

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. extractionextracted with EtOAc three times
  5. concentrationAfter concentrating the combined EtOAc layers
  6. customthe residue was purified by flash chromatography (silica gel, 300 g, 0 to 80% EtOAc/Hexane)

Sources & evidence

ORD record
ord-6b08aa0f3d744230b084b5631f29c42d
Source dataset
uspto-grants-2014_01
Patent number
US08637523B2

Linked notes

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