Tris(1,1-dimethylethyl)phosphine → Methyl 2-(2,6-difluoro-4-methoxy-phenyl)thiazole-4-carboxylate

HRID 521893노트

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HRID 521893 반응식
Br[C:2]1[S:3][CH:4]=[C:5]([C:7]([O:9][CH3:10])=[O:8])[N:6]=1.[F:11][C:12]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([F:20])[C:13]=1B(O)O.[F-].[K+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>O1CCCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:11][C:12]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([F:20])[C:13]=1[C:2]1[S:3][CH:4]=[C:5]([C:7]([O:9][CH3:10])=[O:8])[N:6]=1

참가 물질

8

반응물 4

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 522689Potassium FluorideHCID 2763213Methyl 2-bromothiazole-4-carboxylateHCID 162174242,6-Difluoro-4-methoxybenzeneboronic acid

생성물 1

HCID 86713850Methyl 2-(2,6-difluoro-4-methoxy-phenyl)thiazole-4-carboxylate수율 74%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 8028Tetrahydrofuran용매

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온도
100 °C

실험 절차

To a solution of methyl 2-bromothiazole-4-carboxylate (3.27 mmol, 741 mg) in tetrahydrofuran (15 mL) and water (1.5 mL) was added 2,6-difluoro-4-methoxyphenylboronic acid (1.8 equiv., 5.88 mmol, 1160 mg) and potassium fluoride (3.3 equiv., 10.8 mmol, 627 mg). The mixture was degassed with nitrogen, then tris(dibenzylideneacetone)dipalladium(0) (0.2 equiv., 0.654 mmol, 617 mg) and tri-tert-butylphosphine (1.0 M in toluene; 0.4 equiv., 1.31 mmol, 1.3 mL) were added and the reaction mixture was heated under microwave at 100° C. for 30 minutes. The reaction mixture was concentrated and the residue was purified on silica eluted with 0 to 50% EtOAc in heptane to afford methyl 2-(2,6-difluoro-4-methoxy-phenyl)thiazole-4-carboxylate (2.40 mmol, 685 mg, 74% yield).

후처리

  1. customThe mixture was degassed with nitrogen
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue was purified on silica
  4. washeluted with 0 to 50% EtOAc in heptane

출처 및 근거

ORD 기록
ord-0c202543724941d6853a27b6150abbbb
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09328106B2

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