Toluene → HCID 22714048, compound

HRID 352234Notes

Reaction equation

HRID 352234 reaction equation
[C:1]([NH:9][CH2:10][CH:11]1[CH2:16][CH2:15][CH2:14][CH:13]([N:17]2C3C=CC=C(C(O)=O)C=3[C:20]3=[N:30][O:31][C:32]([CH3:33])=[C:19]3[C:18]2=[O:34])[CH2:12]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=[O:36].C([Zn][CH2:42][CH3:43])C.C([Cu])#N.[Li+].[Cl-].[C:49]1([CH3:55])[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1>C1COCC1.[NH4+].[Cl-]>[CH3:33][C:32]1[O:31][N:30]=[C:20]2[C:54]3[C:49]([C:55](=[O:36])[CH2:42][CH3:43])=[CH:50][CH:51]=[CH:52][C:53]=3[N:17]([CH:13]3[CH2:14][CH2:15][CH2:16][CH:11]([CH2:10][NH:9][C:1](=[O:8])[C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[CH2:12]3)[C:18](=[O:34])[C:19]=12

Participants

9

Reactant 6

HCID 1140TolueneHCID 24386Thionyl ChlorideHCID 433294Lithium ChlorideHCID 22714071HCID 22714071, compoundHCID 178418546HCID 178418546, compoundHCID 178418750HCID 178418750, compound

Product 1

HCID 22714048HCID 22714048, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of Example 598 (0.05 g, 0.011 mmol) in toluene (2 ml) under N2 was added thionyl chloride (1 ml) and heated at reflux for 3 h. The solution was concentrated using toluene to azeotrope. To a solution of diethylzinc (1 ml, 1 mmol) under N2 stirring at −20° C. was added a solution of CuCN (0.093 g, 1.04 mmol) and LiCl (0.086 g, 2.02 mmol) in THF (1.5 ml). This mixture was gradually allowed to warm to 0° C., stirred for 15 min at this temperature, and cooled to −25° C. To this solution was added the acid chloride residue in THF (0.5 ml) and stirred for 1.5 h gradually allowing to warm to 0° C. The reaction was diluted with NH4Cl(aq) and extracted with dichloromethane (2×). The combined organic layers were washed (brine), dried (MgSO4), filtered, and concentrated. Column chromatography (silica gel, acetone/dichloromethane gradient) gave the title compound (0.013 g, 28%).

Workup

  1. temperatureheated
  2. temperatureat reflux for 3 h
  3. concentrationThe solution was concentrated
  4. temperaturecooled to −25° C
  5. stirringstirred for 1.5 h
  6. temperatureto warm to 0° C
  7. extractionextracted with dichloromethane (2×)
  8. washThe combined organic layers were washed (brine)
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-5a91164211184644af52c34fec097e2e
Source dataset
uspto-grants-2004_06
Patent number
US06743794B2

Reaction notes

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