Cesium carbonate → Benzyl 2-(4-(1-(tert-butyldimethylsilyloxy)cyclopropyl)-3-fluorophenyl)acrylate

HRID 1842902노트

반응식

HRID 1842902 반응식
[C:1]([Si:5]([O:8][C:9]1([C:12]2[CH:17]=[CH:16][C:15](B3OC(C)(C)C(C)(C)O3)=[CH:14][C:13]=2[F:27])[CH2:11][CH2:10]1)([CH3:7])[CH3:6])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].Br[C:35](=[CH2:46])[C:36]([O:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:37]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Si:5]([O:8][C:9]1([C:12]2[CH:17]=[CH:16][C:15]([C:35](=[CH2:46])[C:36]([O:38][CH2:39][C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)=[O:37])=[CH:14][C:13]=2[F:27])[CH2:11][CH2:10]1)([C:1]([CH3:2])([CH3:4])[CH3:3])([CH3:7])[CH3:6]

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 13443472Benzyl 2-bromoprop-2-enoateHCID 70815542Tert-butyl(1-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropoxy)-dimethylsilane

생성물 1

HCID 86672144Benzyl 2-(4-(1-(tert-butyldimethylsilyloxy)cyclopropyl)-3-fluorophenyl)acrylate수율 37.2%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 6228Dimethylformamide용매

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온도
95 °C

실험 절차

To a stirred and degassed (degassed with Argon) suspension of tert-butyl(1-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclopropoxy)-dimethylsilane (10.23 g, 26.09 mmol, leg), Cs2CO3 (30.69 g, 78.27 mmol, 3 eq), and benzyl 2-bromoacrylate (9.59 g, 39.14 mmol, 1.5 eq) in DMF (100 mL) was added Pd(dppf)Cl2 (1.06 g, 1.305 mmol, 0.05 eq) and the mixture heated to 90-100° C. for 1 h. The reaction mixture was filtered through celite pad, diluted with water (100 mL) and extracted with ethyl acetate (250 mL). The ethyl acetate layer was washed with water (150 mL), brine (200 mL), dried (Na2SO4) and the solvent evaporated to get crude benzyl 2-(4-(1-(tert-butyldimethylsilyloxy)-cyclopropyl)-3-fluorophenyl)acrylate (4.14 g) as a yellow oil which was used for the next stage without purification (TLC system: EtOAc/PE (1:49), Rf: 0.5).

후처리

  1. customdegassed
  2. filtrationThe reaction mixture was filtered through celite pad
  3. additiondiluted with water (100 mL)
  4. extractionextracted with ethyl acetate (250 mL)
  5. washThe ethyl acetate layer was washed with water (150 mL), brine (200 mL)
  6. dry with materialdried (Na2SO4)
  7. customthe solvent evaporated

출처 및 근거

ORD 기록
ord-edfea75450fa4f58a2b05c4761fbe125
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946204B2

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