Ammonium Chloride → (3-Bromo-6-methoxy-pyrazolo[5,1-b]thiazol-7-yl)-carbamic acid tert-butyl ester

HRID 1971784ノート

反応式

HRID 1971784 の反応式
[CH3:1][O:2][C:3]1[C:10]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[C:6]2[S:7][CH:8]=[CH:9][N:5]2[N:4]=1.C([Li])CCC.[Br:24]C(F)(F)C(F)(F)Br.[Cl-].[NH4+]>CCCCCCC.C(OCC)(=O)C.C(O)(=O)C.C(OCC)(=O)C.C1COCC1>[Br:24][C:9]1[N:5]2[N:4]=[C:3]([O:2][CH3:1])[C:10]([NH:11][C:12](=[O:18])[O:13][C:14]([CH3:15])([CH3:17])[CH3:16])=[C:6]2[S:7][CH:8]=1

参加物

9

反応物 4

HCID 25517Ammonium ChlorideHCID 313011,2-Dibromo-1,1,2,2-tetrafluoroethaneHCID 57912437Tert-butyl (6-methoxypyrazolo[5,1-b][1,3]thiazol-7-yl)carbamateHCID 178418339Butyllithium

生成物 1

HCID 57912433(3-Bromo-6-methoxy-pyrazolo[5,1-b]thiazol-7-yl)-carbamic acid tert-butyl ester収率 66.9%

試薬・触媒・溶媒 4

HCID 176Acetic Acid溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒HCID 21899848Ethylacetate heptane溶媒

反応条件

温度
-78 °C

実験手順

To a mixture of tert-butyl (6-methoxypyrazolo[5,1-b][1,3]thiazol-7-yl)carbamate (16.5 g, 61.4 mmol) and THF (410 mL) was added n-butyllithium (2.77 M solution in n-hexane: 62.1 mL, 172 mmol) while stirring at −78° C. After further stirring the mixture at −78° C. for 40 minutes, 1,2-dibromotetrafluoroethane (10.2 mL, 86 mmol) was added and stirring was continued for 2 hours while heating to room temperature. A saturated aqueous solution of ammonium chloride and ethyl acetate were added to the mixture, and then acetic acid was added to a weakly acidic pH of the mixture. After thoroughly shaking the mixture, the organic layer was separated and the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The mixture was filtered, and then the solvent in the filtrate was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (mixture of n-heptane and ethyl acetate: n-heptane/ethyl acetate=1/0 then 4/1) to obtain the title compound (14.3 g, 41.1 mmol).

後処理

  1. stirringAfter further stirring the mixture at −78° C. for 40 minutes
  2. stirringstirring
  3. temperaturewhile heating to room temperature
  4. stirringAfter thoroughly shaking the mixture
  5. customthe organic layer was separated
  6. washthe organic layer was washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationThe mixture was filtered
  9. distillationthe solvent in the filtrate was distilled off under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (
  11. additionmixture of n-heptane and ethyl acetate

出典と根拠

ORDレコード
ord-87b8f27bf3f840a5871cd43d10445c66
出典データセット
uspto-grants-2013_04
特許番号
US08431603B2

反応ノート

読み込み中…