Thionyl Chloride → HCID 66713131, compound

HRID 1406203Notes

Reaction equation

HRID 1406203 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[C:3]1[C:17](O)=[O:18].O=S(Cl)Cl.Cl.[CH3:25][O:26][C:27](=[O:30])[CH2:28][NH2:29]>CCN(CC)CC>[CH3:25][O:26][C:27](=[O:30])[CH2:28][NH:29][C:2]([C:3]1[C:17](=[O:18])[C:16]2[C:11]([C:4]=1[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[CH:12][CH:13]=[CH:14][CH:15]=2)=[O:1]

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 122755Glycine methyl ester hydrochlorideHCID 12424767HCID 12424767, compound

Product 1

HCID 66713131HCID 66713131, compoundYield 101.4%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

A mixture of 1-oxo-3-phenyl-1H-indene-2-carboxylic acid (2.13 g, 8.5 mmol; can be obtained according to M. R. Barvian et al. in Bioorg. Med. Chem. Lett. 1997, 7, 2903-2908) and SOCl2 (17 ml) was refluxed with stirring for 15 min. Excess SOCl2 was then evaporated in vacuo. The residue was dissolved in anhydrous CH2Cl2 (20 ml), and subsequently the solution was concentrated in vacuo again to remove last traces of SOCl2. The residue was dissolved in anhydrous CH2Cl2 (20 ml). The solution was cooled with an ice bath before glycine methyl ester hydrochloride (1.27 g, 10 mmol) and subsequently NEt3 (3.52 ml, 25 mmol, dropwise addition) were added with stirring. The ice bath was then removed and stirring was continued at ambient temperature for 45 min before the mixture was concentrated in vacuo. To the residue was added water (10 ml) and aqueous 2N HCl (15 ml) and the mixture was extracted with ethyl acetate (1×70 ml). The organic phase was dried over MgSO4 and evaporated in vacuo to give an orange solid (2.77 g). Purification by flash column chromatography on silica gel using hexanes:EtOAc=2:1 as the eluent gave the title compound as an orange solid (2.11 g); MS-(+)-ion: M+1=322.0.

Workup

  1. temperaturewas refluxed
  2. customExcess SOCl2 was then evaporated in vacuo
  3. dissolutionThe residue was dissolved in anhydrous CH2Cl2 (20 ml)
  4. concentrationsubsequently the solution was concentrated in vacuo again
  5. customto remove last traces of SOCl2
  6. dissolutionThe residue was dissolved in anhydrous CH2Cl2 (20 ml)
  7. addition3.52 ml, 25 mmol, dropwise addition)
  8. additionwere added
  9. stirringwith stirring
  10. customThe ice bath was then removed
  11. stirringstirring
  12. waitwas continued at ambient temperature for 45 min before the mixture
  13. concentrationwas concentrated in vacuo
  14. additionTo the residue was added water (10 ml) and aqueous 2N HCl (15 ml)
  15. extractionthe mixture was extracted with ethyl acetate (1×70 ml)
  16. dry with materialThe organic phase was dried over MgSO4
  17. customevaporated in vacuo

Sources & evidence

ORD record
ord-48359f2dbe1e4df199e83eace9ae9d59
Source dataset
uspto-grants-2014_12
Patent number
US08916585B2

Reaction notes

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