Xenon difluoride → N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(fluoromethylthio)-benzamide

HRID 356898ノート

反応式

HRID 356898 の反応式
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:25])[C:7]=1[NH:8][C:9](=[O:24])[C:10]1[CH:15]=[CH:14][C:13]([S:16][CH3:17])=[C:12]([O:18][CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[CH:11]=1.C(C1C=C(C)C=C(C(C)(C)C)N=1)(C)(C)C.[Xe](F)[F:42]>ClCCl>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:25])[C:7]=1[NH:8][C:9](=[O:24])[C:10]1[CH:15]=[CH:14][C:13]([S:16][CH2:17][F:42])=[C:12]([O:18][CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[CH:11]=1

参加物

5

反応物 3

HCID 83674Xenon difluorideHCID 988982,6-Di-tert-butyl-4-methylpyridineHCID 15458418N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(methylthio)benzamide

生成物 1

HCID 21187859N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(fluoromethylthio)-benzamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

A solution of N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(methylthio)benzamide (1 g; that is prepared as described in Example 20) in dichloromethane (100 mL), containing molecular sieve 4A, under nitrogen, is treated with 2,6-di-tert-butyl-4-methylpyridine (1.28 g). The resulting mixture is stirred at room temperature for 1.5 hours, and then it is cooled to 0° C. (in an ice/salt bath) and treated with xenon difluoride (0.51 g) in one portion. After stirring for a further 2 hours in the cold, the mixture is filtered, and the filtrate is washed with saturated aqueous ammonium chloride solution. The organic phase is dried over sodium sulfate and evaporated. The resulting residue is subjected to flash chromatography, eluting with a mixture of ethyl acetate and pentane (2:3 v/v), to give impure N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(fluoromethylthio)-benzamide (600 mg). It is further purified by reversed phase HPLC on octadecylsilyl silica gel, eluting with a mixture of methanol and water (7:3 v/v), to give N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-(fluoromethylthio)benzamide (519 mg), in the form of a white solid, m.p. 111°-113° C. [Elemental analysis: C,51.50; H,4.12; N,6.74%; calculated: C,52.05; H,4.12; N,6.74%].

後処理

  1. customthat is prepared
  2. temperatureit is cooled to 0° C. (in an ice/salt bath)
  3. stirringAfter stirring for a further 2 hours in the cold, the mixture
  4. filtrationis filtered
  5. washthe filtrate is washed with saturated aqueous ammonium chloride solution
  6. dry with materialThe organic phase is dried over sodium sulfate
  7. customevaporated
  8. washeluting with a mixture of ethyl acetate and pentane (2:3 v/v)

出典と根拠

ORDレコード
ord-51b96e48d58549ea9dbc0bbf5de794e5
出典データセット
uspto-grants-1998_11
特許番号
US05840724

反応ノート

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