3,3,3-Triethoxyprop-1-yne → ethyl 4-(2-chloro-6-(3,3,3-triethoxyprop-1-ynyl)phenyl)-tetrahydro-2H-pyran-4-carboxylate

HRID 1868937Notes

Reaction equation

HRID 1868937 reaction equation
Br[CH2:2][CH2:3][O:4][CH2:5][CH2:6][CH:7]([C:13]1[C:18](I)=[CH:17][CH:16]=[CH:15][C:14]=1[Cl:20])[C:8]([O:10][CH2:11][CH3:12])=[O:9].[CH2:21]([O:23][C:24]([O:30][CH2:31][CH3:32])([O:27][CH2:28][CH3:29])[C:25]#[CH:26])[CH3:22]>C(#N)C.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:20][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]([C:26]#[C:25][C:24]([O:27][CH2:28][CH3:29])([O:23][CH2:21][CH3:22])[O:30][CH2:31][CH3:32])[C:13]=1[C:7]1([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

7

Reactant 2

HCID 109209723,3,3-Triethoxyprop-1-yneHCID 67100121Ethyl α-[2-(2-bromoethoxy)ethyl]-2-chloro-6-iodobenzeneacetate

Product 1

HCID 67100193ethyl 4-(2-chloro-6-(3,3,3-triethoxyprop-1-ynyl)phenyl)-tetrahydro-2H-pyran-4-carboxylateYield 45.9%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of ethyl 4-(2-bromoethoxy)-2-(2-chloro-6-iodophenyl)butanoate (5.8 g, 12 mmol) and TEA (15 mL, 110 mmol) in 24 mL ACN was degassed by vacuum and back filled with nitrogen 3 times. The mixture was treated with 3,3,3-triethoxyprop-1-yne (2.7 g, 16 mmol), dichlorobis(triphenylphosphine)palladium(ii) (0.17 g, 0.24 mmol) and copper(I) iodide (0.12 g, 0.61 mmol). The mixture was stirred at 55° C. for 2 hours. The mixture was cooled to room temperature, diluted with 100 mL EtOAc, and washed with water (3×20 mL) and then with 20 mL saturated NaCl. The organic layers were dried and concentrated. The crude product was evaporated from 50 mL toluene and dissolved in 50 mL DMF. The mixture was treated with 0.7 g NaH. The mixture was stirred at room temperature for 15 hours. The mixture was quenched with 50 mL water and neutralized with 10% HCl to pH=5. The mixture was then extracted with ether (3×100 mL). The combined organic layers were washed with water (3×20 mL) and saturated NaCl (20 mL), and then dried over anhydrous sodium sulfate and concentrated. The crude product was purified by column chromatography (10% EtOAc/hexane) to give 2.42 g yellow oil. MS m/e: (M+H)+ 487.

Workup

  1. customwas degassed by vacuum
  2. additionback filled with nitrogen 3 times
  3. temperatureThe mixture was cooled to room temperature
  4. washwashed with water (3×20 mL)
  5. customThe organic layers were dried
  6. concentrationconcentrated
  7. customThe crude product was evaporated from 50 mL toluene
  8. dissolutiondissolved in 50 mL DMF
  9. additionThe mixture was treated with 0.7 g NaH
  10. stirringThe mixture was stirred at room temperature for 15 hours
  11. customThe mixture was quenched with 50 mL water and neutralized with 10% HCl to pH=5
  12. extractionThe mixture was then extracted with ether (3×100 mL)
  13. washThe combined organic layers were washed with water (3×20 mL) and saturated NaCl (20 mL)
  14. dry with materialdried over anhydrous sodium sulfate
  15. concentrationconcentrated
  16. customThe crude product was purified by column chromatography (10% EtOAc/hexane)

Sources & evidence

ORD record
ord-637706de6e044d058c45ba02081c2e13
Source dataset
uspto-grants-2009_12
Patent number
US07635715B2

Reaction notes

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