Dichloromethane → Ethyl (2E)-3-[3-chloro-6-ethoxy-2-fluoro-5-(2-methyl-1,3-dioxolan-2-yl)phenyl]acrylate

HRID 1499952Notes

Reaction equation

HRID 1499952 reaction equation
[Cl:1][C:2]1[C:3]([F:18])=[C:4](I)[C:5]([O:14][CH2:15][CH3:16])=[C:6]([C:8]2([CH3:13])[O:12][CH2:11][CH2:10][O:9]2)[CH:7]=1.CC1(C)C(C)(C)OB(/[CH:27]=[CH:28]/[C:29]([O:31][CH2:32][CH3:33])=[O:30])O1.C(=O)([O-])[O-].[K+].[K+].ClCCl>O1CCOCC1.O>[Cl:1][C:2]1[C:3]([F:18])=[C:4](/[CH:27]=[CH:28]/[C:29]([O:31][CH2:32][CH3:33])=[O:30])[C:5]([O:14][CH2:15][CH3:16])=[C:6]([C:8]2([CH3:13])[O:12][CH2:11][CH2:10][O:9]2)[CH:7]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 23553751(E)-Ethyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylateHCID 866778682-(5-Chloro-2-ethoxy-4-fluoro-3-iodophenyl)-2-methyl-1,3-dioxolane

Product 1

HCID 86677867Ethyl (2E)-3-[3-chloro-6-ethoxy-2-fluoro-5-(2-methyl-1,3-dioxolan-2-yl)phenyl]acrylateYield 96.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-(5-chloro-2-ethoxy-4-fluoro-3-iodophenyl)-2-methyl-1,3-dioxolane (22 g, 58 mmol) (from Step 1), ethyl (2E)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)acrylate (16 mL, 70 mmol), and potassium carbonate (24 g, 170 mmol) in 1,4-dioxane (230 mL) and water (110 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) (2.4 g, 2.9 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 (300 mL). The filtrate was poured into water (400 mL). The aqueous layer was separated and extracted with additional ethyl acetate (300 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated to a crude brown solid. The crude material was purified by flash column chromatography using ethyl acetate in hexanes (0%-30%) to give the desired product (20 g, 96%). 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J=16.5 Hz, 1H), 7.56 (d, J=8.6 Hz, 1H), 6.70 (dd, J=16.5, 0.9 Hz, 1H), 4.26 (q, J=7.1 Hz, 2H), 4.10-3.99 (m, 2H), 3.91 (q, J=7.0 Hz, 2H), 3.87-3.76 (m, 2H), 1.73 (s, 3H), 1.44 (t, J=7.0 Hz, 3H), 1.33 (t, J=7.1 Hz, 3H). LCMS 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 (300 mL)
  5. additionThe filtrate was poured into water (400 mL)
  6. customThe aqueous layer was separated
  7. extractionextracted with additional ethyl acetate (300 mL)
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated to a crude brown solid
  12. customThe crude material was purified by flash column chromatography

Sources & evidence

ORD record
ord-32b398b5fde94919aa23a878c8bb5bda
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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