HCID 10686296, compound → HCID 54258722, compound

HRID 2255023Notes

Reaction equation

HRID 2255023 reaction equation
I[CH2:2][CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].Br[C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([CH2:16][O:17][CH2:18][CH2:19][C:20]#[C:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH:11]=1>C1(C)C=CC=CC=1.CN(C)C(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:18]([O:17][CH2:16][C:12]1[CH:11]=[CH:10][C:15]([CH2:2][CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])=[CH:14][CH:13]=1)[CH2:19][C:20]#[C:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]

Participants

6

Reactant 2

HCID 10686296HCID 10686296, compoundHCID 10911297Ethyl 3-iodopropanoate

Product 1

HCID 54258722HCID 54258722, compoundYield 51%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent3×HCID 31374DimethylacetamideSolvent

Procedure

A flask was charged with Zn-Cu couple (200 mg, 3 mmol) solution of ethyl 3-iodopropanoate (510 mg, 2 mmol) in dry toluene (4 mL) and dry N,N-dimethylacetamide (2mL) was added. The mixture was vigorously stirred for 1 hour at room temperature and then heated at gentle reflux for 4.5 hours. After the mixture was cooled to 60° C, a solution of tetrakis(triphenylphosphine)palladium(0)(30 mg, 0.026 mmol) in toluene (2 mL) was added over 1 minute and stirring was continued for 5 minutes at the same temperature. A solution of (45) (309 mg, 1 mmol) in dry toluene (2 mL) was added and the mixture was refluxed for 12 hours. The reaction mixture was allowed to cool to 25° C. and filtered through a Celite pad. The filter cake was washed with ether (50 mL). The filtrate was successively washed with a solution of i N ammonium chloride (10 mL), a solution of saturated sodium hydrogen carbonate (10 mL) and a solution of saturated sodium chloride (10 mL). The aqueous phases were back extracted with ether (30 mL), the combined organic extracts were dried (MgSO4), filtered, concentrated by rotary evaporation to yield a yellow oil. Purification by flash silica gel chromatography (97:03 petroleum ether/EtOAc) afforded (46) (165 mg, 51%) as a colorless oil: Rf 0.44 (95:05 petroleum ether/EtOAc); 1H NMR (CDCl3) δ 7.19 (m, 4 H), 4.51 (s, 2 H), 4.12 (q, J=7.2 Hz, 2 H), 3.55 (t, J=7.2 Hz, 2 H), 2.94 (t, J=8.1 Hz, 2 H), 2.61 (t, J=8.1 Hz, 2 H), 2.46 (tt, J1 =6.9 Hz, J2 =2.1 Hz, 2 H), 2.13 (tt, J1 =7.2 Hz, J2 =2.4 Hz, 2 H), 1.40 (m, 6 H), 1.22 (t, J=7.2 Hz, 3 H), 0.88 (t, J=6.9 Hz, 3 H); 13C NMR (CDCl3) δ 173.01, 140.87, 138.58, 128.68, 127.75, 81.64, 76.67, 72.99, 69.15, 60.53, 36.02, 31.01, 31.18, 28.81, 22.34, 20.28, 18.85, 14.32, 14.12. ##STR14##

Workup

  1. additionwas added
  2. temperatureheated
  3. temperatureat gentle reflux for 4.5 hours
  4. temperatureAfter the mixture was cooled to 60° C
  5. stirringstirring
  6. waitwas continued for 5 minutes at the same temperature
  7. temperaturethe mixture was refluxed for 12 hours
  8. temperatureto cool to 25° C.
  9. filtrationfiltered through a Celite pad
  10. washThe filter cake was washed with ether (50 mL)
  11. washThe filtrate was successively washed with a solution of i N ammonium chloride (10 mL)
  12. extractionThe aqueous phases were back extracted with ether (30 mL)
  13. dry with materialthe combined organic extracts were dried (MgSO4)
  14. filtrationfiltered
  15. concentrationconcentrated by rotary evaporation
  16. customto yield a yellow oil
  17. customPurification by flash silica gel chromatography (97:03 petroleum ether/EtOAc)

Sources & evidence

ORD record
ord-33fb7f67069a4703ba11aae0422508c3
Source dataset
uspto-grants-1993_08
Patent number
US05238832

Reaction notes

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