反応式
C1(C[O:5]C2C=C(C=CC=2O)C=O)CC1.ClC(F)F.[OH-].[Na+].[CH:21]1([CH2:24][O:25][C:26]2[CH:27]=[C:28]([CH:31]=[CH:32][C:33]=2[O:34][CH:35]([F:37])[F:36])[CH:29]=[O:30])[CH2:23][CH2:22]1.Cl([O-])=O.[Na+].S(=O)(=O)(O)N>[Cl-].C([N+](C)(C)C)C1C=CC=CC=1>[CH:21]1([CH2:24][O:25][C:26]2[CH:27]=[C:28]([CH:31]=[CH:32][C:33]=2[O:34][CH:35]([F:36])[F:37])[C:29]([OH:5])=[O:30])[CH2:23][CH2:22]1参加物
8
反応物 6
生成物 1
試薬・触媒・溶媒 1
実験手順
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.
出典と根拠
- ORDレコード
- ord-44521b88145e401fb7e3c0db6db891fd
- 出典データセット
- uspto-grants-2016_04
- 特許番号
- US09321726B2
関連ノート
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