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

HRID 1971784

반응식

HRID 1971784 반응식
[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

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 4

HCID 176Acetic Acid용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매HCID 21899848Ethylacetate heptane용매

반응 조건

온도
-78 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-87b8f27bf3f840a5871cd43d10445c66
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431603B2

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