Sulfuric Acid → Methyl 5-amino-4-fluoro-1H-benzimidazole-6-carboxylate

HRID 391266ノート

反応式

HRID 391266 の反応式
[NH2:1][C:2]1[C:11]([F:12])=[C:10]([NH2:13])[C:9]([NH2:14])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH:15](OCC)(OCC)OCC.OS(O)(=O)=O>C1COCC1>[CH3:7][O:6][C:4]([C:3]1[C:2]([NH2:1])=[C:11]([F:12])[C:10]2[N:13]=[CH:15][NH:14][C:9]=2[CH:8]=1)=[O:5]

参加物

5

反応物 3

HCID 1118Sulfuric AcidHCID 31214Ethyl orthoformateHCID 59365495Methyl 2,4,5-triamino-3-fluorobenzoate

生成物 1

HCID 59365501Methyl 5-amino-4-fluoro-1H-benzimidazole-6-carboxylate収率 94.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

To a stirred solution of methyl 2,4,5-triamino-3-fluorobenzoate (9) (7.58 g, 38.1 mmol) in THF (152 mL, 20 vol) was added triethyl orthoformate (20.3 g, 22.8 mL, 137.0 mmol), followed by dropwise addition of H2SO4 (9.33 g, 18 M, 94.1 mmol). The mixture was then heated at 60° C. for 6 hours, at which point no starting material was detected by HPLC analysis. The solid product was filtered and rinsed with THF (150 mL, 20 vol), then transferred to a reaction vessel, suspended in water (150 mL) and the resulting mixture was neutralized to about pH 7.5 with 2 N NaOH. After stirring for 30 minutes, the suspension was filtered and the solid product was dried in a vacuum oven at 55° C., overnight to provide 6-amino-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester (12) 7.5 g, 94% yield (100% area by HPLC). 1H NMR (400 Hz, d6 DMSO) δ 3.53 (1H, br s, NH), 3.85, (3H, s, OMe), 6.10 (2H, br s, NH2), 7.90 (1H, s, Ar—H), 7.20 (1H, s, Ar—H). MS APCI (+) m/z 210 (M+1) detected with MS APCI (+).

後処理

  1. filtrationThe solid product was filtered
  2. washrinsed with THF (150 mL, 20 vol)
  3. customtransferred to a reaction vessel
  4. filtrationthe suspension was filtered
  5. customthe solid product was dried in a vacuum oven at 55° C., overnight

出典と根拠

ORDレコード
ord-56544fb05b6849f1be4c8cf53ad9ef60
出典データセット
uspto-grants-2013_02
特許番号
US08383832B2

反応ノート

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