化工社化工社 化学情報印刷レポート · 研究参考用
Sulfamic Acid → 3-(Cyclopropylmethoxy)-4-(difluoromethoxy)benzoic Acid
関与物質
| 役割 | 名称 | HCID | 仕込み量 |
|---|---|---|---|
| 反応物 | Sulfamic Acid | HCID 5987 | — |
| 反応物 | Chlorodifluoromethane | HCID 6372 | — |
| 反応物 | Sodium Hydroxide | HCID 14798 | — |
| 反応物 | 3-(Cyclopropylmethoxy)-4-(difluoromethoxy)benzaldehyde | HCID 18973698 | — |
| 反応物 | Sodium Chlorite | HCID 23668197 | — |
| 反応物 | 3-(Cyclopropylmethoxy)-4-hydroxybenzaldehyde | HCID 71302977 | — |
| 触媒 | Benzyltrimethylammonium chloride | HCID 5963 | — |
| 生成物 | 3-(Cyclopropylmethoxy)-4-(difluoromethoxy)benzoic Acid | HCID 2394006 | — |
反応手順
In WO9501338 the reaction of 3-(cyclopropylmethoxy)-4-hydroxy-benzaldehyde with chlorodifluoromethane in the presence of sodium hydroxide and benzyl-trimethylammonium chloride (BTMA) in dioxane/water leads to 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzaldehyde, which by oxidation with sodium chlorite and sulphamic acid yields 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzoic acid. Chlorination of this acid with thionyl chloride in reflux toluene provides the corresponding acyl chloride, which is finally condensed with 3,5-dichloropyridine-4-amine in the presence of sodium hydride in tetrahydrofuran to thus reach roflumilast (I). These procedures are set out in Scheme 1.
情報源と証拠
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|---|
| 特許番号 | US09321726B2 |
| 出典データセット | uspto-grants-2016_04 |
| ORD ID | ord-44521b88145e401fb7e3c0db6db891fd |
| 出典メモ | uspto-grants-2016_04 |