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Sodium hydride → 4-Chloro-2-[(2,3-difluorophenyl)methylthio]-6-{(1R)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethoxy}pyrimidine

HRID 1958961
ノート
印刷プレビュー

反応式

HRID 1958961 の反応式
[CH3:1][C:2]1([CH3:10])[O:6][C@@H:5]([C@H:7]([OH:9])[CH3:8])[CH2:4][O:3]1.[H-].[Na+].[Cl:13][C:14]1[CH:19]=[C:18](Cl)[N:17]=[C:16]([S:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:24]=2[F:30])[N:15]=1>C1COCC1>[Cl:13][C:14]1[CH:19]=[C:18]([O:9][C@@H:7]([C@H:5]2[CH2:4][O:3][C:2]([CH3:10])([CH3:1])[O:6]2)[CH3:8])[N:17]=[C:16]([S:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:24]=2[F:30])[N:15]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 12241285(1R)-1-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]ethanol2 回HCID 859280374,6-Dichloro-2-((2,3-difluorobenzyl)thio)pyrimidine

生成物 1

HCID 866198804-Chloro-2-[(2,3-difluorophenyl)methylthio]-6-{(1R)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethoxy}pyrimidine

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran
溶媒

実験手順

To a solution of (1R)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]ethanol (the product of step iv) (0.24 g) in dry THF (10 mL) at 0° C. was added in portions sodium hydride (91 mg as 60% dispersion in mineral oil) followed in portions by 4,6-dichloro-2-[(2,3-difluorobenzyl)thio]pyrimidine (the product of example 1 step ii) (0.50 g). The reaction mixture was stirred at room temperature for 48 h then quenched with saturated aqueous ammonium chloride (10 mL) and diluted with ethyl acetate. The layers were separated and the aqueous layer extracted with further ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography on silica gel using EtOAc/isohexane (1:19 to 1:9 gradient) as eluent to give the subtitle compound as a pale yellow solid. Yield: 0.42 g.

後処理

  1. customthen quenched with saturated aqueous ammonium chloride (10 mL)
  2. additiondiluted with ethyl acetate
  3. customThe layers were separated
  4. extractionthe aqueous layer extracted with further ethyl acetate
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by column chromatography on silica gel

出典と根拠

ORDレコード
ord-5b2bb2665cc744ab9c0b5e18fcd200cb
出典データセット
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08410123B2

反応ノート

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