4-Nitrophenyl chloroformate → HCID 66969074, compound

HRID 1189529Notes

Reaction equation

HRID 1189529 reaction equation
[CH3:1][NH:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:13]=[CH:12][N:11]([C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)[N:10]=2)=[CH:5][CH:4]=1.Cl[C:26]([O:28][C:29]1[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][CH:30]=1)=[O:27]>C1COCC1>[N+:35]([C:32]1[CH:33]=[CH:34][C:29]([O:28][C:26](=[O:27])[N:2]([CH3:1])[C:3]2[CH:8]=[CH:7][C:6]([C:9]3[N:13]=[CH:12][N:11]([C:14]4[CH:19]=[CH:18][C:17]([O:20][C:21]([F:22])([F:24])[F:23])=[CH:16][CH:15]=4)[N:10]=3)=[CH:5][CH:4]=2)=[CH:30][CH:31]=1)([O-:37])=[O:36]

Participants

4

Reactant 2

HCID 821294-Nitrophenyl chloroformateHCID 66969086HCID 66969086, compound

Product 1

HCID 66969074HCID 66969074, compoundYield 60.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A suspension of 4-[1-(4-trifluoroethyloxyphenyl)-1H-[1,2,4]triazol-3-yl]-phenylamine (1.2 g, 3.7 mmol) in EtOH (4 mL) was treated with 1H-benzotriazole (0.48 g, 4.0 mmol) and formaldehyde (0.5 mL of 37% aqueous, 6 mmol), and the solution was heated to 40° C. for 10 min. Upon cooling, a solid formed, which was collected by filtration. There was obtained 1.33 g of the triazole adduct as a light yellow solid, mp 185-187° C. This material (1.2 g, 2.66 mmol) was dissolved in THF (20 mL) and treated with NaBH4 (0.11 g, 2.9 mmol). The solution was stirred at ambient temperature for 30 min, then heated to reflux for 1 h. After cooling, the solution was poured onto water (30 mL) and extracted with ether. Drying and concentration, followed by silica gel chromatography (75:25 Hexanes:EtOAc) furnished methyl-{4-[1-(4-trifluoromethoxyphenyl)-1H-[1,2,4]triazol-3-yl]-phenyl}-amine (0.76 g, 86%) as a white solid, mp 121-123° C.; 1H NMR (300 MHz, CDCl3) δ 8.51 (s, 1H), 8.02 (d, J=8.8 Hz, 2H), 7.78 (d, J=9.1 Hz, 2H), 7.37 (d, J=8.3 Hz, 2H), 6.68 (d, J=8.8 Hz, 2H), 3.96 (s, 1H), 2.91 (s, 3H); EIMS m/z 499 (M+). A portion of this amine (0.11 g, 0.33 mmol) was dissolved in dry THF (2 mL) and treated with 4-nitrophenyl chloroformate (0.069 g, 0.34 mmol). The solid which formed over 10 min was collected by filtration and air-dried to give an off-white solid (0.10 g): mp 145-147° C.; 1H NMR (300 MHz, CDCl3) δ 8.59 (s, 1H), 8.28 (d, J=8 Hz, 4H), 7.8 (d, J=8 Hz, 2H), 7.50-7.3 (m, 6H) 3.55 (s, 3H); EIMS m/z 499 (M+).

Workup

  1. customThe solid which formed over 10 min
  2. filtrationwas collected by filtration
  3. customair-dried

Sources & evidence

ORD record
ord-143d7ecc884044b1a277a9a31c58c2db
Source dataset
uspto-grants-2014_03
Patent number
US08674109B2

Reaction notes

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