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

HRID 571032ノート

反応式

HRID 571032 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-e982a0cb2192494ea0e985ae875cca8a
出典データセット
uspto-grants-2015_05
特許番号
US09024040B2

反応ノート

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