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

HRID 1842902Notes

Reaction equation

HRID 1842902 reaction equation
[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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

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

Conditions

Temperature
95 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-edfea75450fa4f58a2b05c4761fbe125
Source dataset
uspto-grants-2015_02
Patent number
US08946204B2

Reaction notes

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