(Z)-3-(Tributylstannyl)prop-2-en-1-ol → (Z)-methyl 3-bromo-6-((4-fluoro-2-(3-hydroxyprop-1-enyl)benzenesulfonyl)methyl)-2-methoxybenzoate

HRID 2177816Notes

Reaction equation

HRID 2177816 reaction equation
[Br:1][C:2]1[C:3]([O:24][CH3:25])=[C:4]([C:9]([CH2:12][S:13]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=2Br)(=[O:15])=[O:14])=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].C([Sn](CCCC)(CCCC)/[CH:31]=[CH:32]\[CH2:33][OH:34])CCC>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Br:1][C:2]1[C:3]([O:24][CH3:25])=[C:4]([C:9]([CH2:12][S:13]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=2/[CH:31]=[CH:32]\[CH2:33][OH:34])(=[O:15])=[O:14])=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

5

Reactant 2

HCID 9974944(Z)-3-(Tributylstannyl)prop-2-en-1-olHCID 66685956Methyl 3-bromo-6-(2-bromo-4-fluorobenzenesulfonylmethyl)-2-methoxybenzoate2×

Product 1

HCID 69915013(Z)-methyl 3-bromo-6-((4-fluoro-2-(3-hydroxyprop-1-enyl)benzenesulfonyl)methyl)-2-methoxybenzoateYield 22.7%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
30 °C

Procedure

A mixture of methyl 3-bromo-6-(2-bromo-4-fluorobenzenesulphonylmethyl)-2-methoxybenzoate (Intermediate 163, 0.916 g), 3-tributylstannyl-(Z)-prop-2-en-1-ol (prepared according to Webb et al, Tetrahedron, 2008, 64, 4778, 0.833 g) and tris(dibenzylideneacetone)dipalladium (0) (0.085 g) in toluene (12 ml) was degassed with argon. Tri-tert-butylphosphine (1M in toluene, 0.20 ml) was added and the mixture was again degassed then heated to 30° C. for 3 hours. After cooling, the mixture was diluted with ethyl acetate and filtered through a PTFE cone. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and pentane containing 1% triethylamine with a gradient of 0-100%, to give (Z)-methyl 3-bromo-6-((4-fluoro-2-(3-hydroxyprop-1-enyl)benzenesulfonyl)methyl)-2-methoxybenzoate (0.198 g) as a yellow oil.

Workup

  1. customwas degassed with argon
  2. additionTri-tert-butylphosphine (1M in toluene, 0.20 ml) was added
  3. customthe mixture was again degassed
  4. temperatureAfter cooling
  5. additionthe mixture was diluted with ethyl acetate
  6. filtrationfiltered through a PTFE cone
  7. customThe filtrate was evaporated to dryness
  8. customthe residue was purified by chromatography on silica
  9. washeluting with a mixture of ethyl acetate and pentane containing 1% triethylamine with a gradient of 0-100%

Sources & evidence

ORD record
ord-9fa368d44a7446d596c7b295b432c170
Source dataset
uspto-grants-2015_06
Patent number
US09067905B2

Reaction notes

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