Lawesson's reagent → (R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-1,4-oxazepane-3-thione

HRID 331135ノート

反応式

HRID 331135 の反応式
[F:1][C:2]1([F:26])[C:8]([CH3:10])([CH3:9])[O:7][CH2:6][C:5](=O)[NH:4][C@@:3]1([C:13]1[CH:18]=[C:17]([C:19]2[CH:20]=[N:21][CH:22]=[N:23][CH:24]=2)[CH:16]=[CH:15][C:14]=1[F:25])[CH3:12].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:36])=CC=1.C(=O)([O-])O.[Na+]>O1CCOCC1>[F:1][C:2]1([F:26])[C:8]([CH3:10])([CH3:9])[O:7][CH2:6][C:5](=[S:36])[NH:4][C@@:3]1([C:13]1[CH:18]=[C:17]([C:19]2[CH:20]=[N:21][CH:22]=[N:23][CH:24]=2)[CH:16]=[CH:15][C:14]=1[F:25])[CH3:12]

参加物

5

反応物 3

HCID 87949Lawesson's reagentHCID 516892Sodium BicarbonateHCID 68380253(R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-1,4-oxazepan-3-one

生成物 1

HCID 86671875(R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-1,4-oxazepane-3-thione収率 111.1%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

A solution of (R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-1,4-oxazepan-3-one (263 mg, 720 μmol) in dioxane (24.0 ml) was treated at room temperature with Lawesson's reagent (233 mg, 576 μmol). The reaction mixture was stirred at 80° C. for 4 hours. For the workup, the reaction mixture was poured on a saturated solution of sodium hydrogencarbonate then extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulphate, filtered and evaporated at reduced pressure to give brown oil. This residue was purified by chromatography on silica gel using a gradient of heptane/dichloromethane=100:0 to 20:80. The (R)-6,6-difluoro-5-(2-fluoro-5-(pyrimidin-5-yl)phenyl)-5,7,7-trimethyl-1,4-oxazepane-3-thione (244 mg, 89% yield) was obtained as a white foam. MS (ISP): m/z=382.1 [M+H]+.

後処理

  1. extractionthen extracted twice with ethyl acetate
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. customevaporated at reduced pressure
  6. customto give brown oil
  7. customThis residue was purified by chromatography on silica gel using a gradient of heptane/dichloromethane=100:0 to 20:80

出典と根拠

ORDレコード
ord-2d20527775864a45a5b788d25c781d1e
出典データセット
uspto-grants-2014_11
特許番号
US08877744B2

反応ノート

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