Dichloromethane → Ethyl 2-[4-chloro-3-fluoro-6-(2-methyl-1,3-dioxolan-2-yl)-2-vinylphenoxy]propanoate

HRID 626858Notes

Reaction equation

HRID 626858 reaction equation
[Cl:1][C:2]1[CH:15]=[C:14]([C:16]2([CH3:21])[O:20][CH2:19][CH2:18][O:17]2)[C:5]([O:6][CH:7]([CH3:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:4](I)[C:3]=1[F:23].[CH3:24][C:25]1(C)C(C)(C)OB(C=C)O1.C(=O)([O-])[O-].[K+].[K+].ClCCl>O1CCOCC1.O>[Cl:1][C:2]1[CH:15]=[C:14]([C:16]2([CH3:21])[O:20][CH2:19][CH2:18][O:17]2)[C:5]([O:6][CH:7]([CH3:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:4]([CH:24]=[CH2:25])[C:3]=1[F:23]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86697549Ethyl 2-[4-chloro-3-fluoro-2-iodo-6-(2-methyl-1,3-dioxolan-2-yl)phenoxy]propanoate

Product 1

HCID 86697550Ethyl 2-[4-chloro-3-fluoro-6-(2-methyl-1,3-dioxolan-2-yl)-2-vinylphenoxy]propanoateYield 157.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of ethyl 2-[4-chloro-3-fluoro-2-iodo-6-(2-methyl-1,3-dioxolan-2-yl)phenoxy]propanoate (1.83 g, 3.99 mmol), 4,4,5,5-tetramethyl-2-vinyl-1,3,2-dioxaborolane (0.880 mL, 5.19 mmol), and potassium carbonate (1.65 g, 12.0 mmol) in 1,4-dioxane (15.6 mL) and water (7.8 mL) was degassed with nitrogen for 10 min. The reaction mixture was treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (163 mg, 0.199 mmol), degassed with nitrogen for another 10 min, and heated at 80° C. for 2 h. The reaction mixture was filtered through Celite and washed with ethyl acetate. The filtrate was poured into water. The aqueous layer was separated and re-extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated give a crude residue. Purification by flash column chromatography (100% hexanes to 15% EtOAc/hexanes) gave the desired product (2.25 g, 57%) as a mixture of enantiomers. LCMS calculated for C17H21ClFO5 (M+H)+: m/z=359.1; found: 359.1.

Workup

  1. customwas degassed with nitrogen for 10 min
  2. customdegassed with nitrogen for another 10 min
  3. filtrationThe reaction mixture was filtered through Celite
  4. washwashed with ethyl acetate
  5. additionThe filtrate was poured into water
  6. customThe aqueous layer was separated
  7. extractionre-extracted with ethyl acetate
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customgive a crude residue
  13. customPurification by flash column chromatography (100% hexanes to 15% EtOAc/hexanes)

Sources & evidence

ORD record
ord-188e84f3651d463bb1927cd91af14529
Source dataset
uspto-grants-2016_04
Patent number
US09309251B2

Reaction notes

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