Hydrochloric Acid → HCID 67273507, compound

HRID 599502Notes

Reaction equation

HRID 599502 reaction equation
[Br-].[CH2:2]([O:4][C:5]([CH2:7][NH+:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10](N2CCCC2)[C:9]1=C)=[O:6])[CH3:3].[C:23]([CH2:25][C:26]([O:28]C(C)(C)C)=[O:27])#[N:24].[CH3:33]C[O-].[Na+].Cl.FC(F)(F)C(O)=O>C(Cl)(Cl)Cl.CCO.CCOC(C)=O.O>[C:23]([C:25](=[CH:33][C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:8]([CH2:7][C:5]([O:4][CH2:2][CH3:3])=[O:6])[CH:9]=1)[C:26]([OH:28])=[O:27])#[N:24]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 70693tert-Butyl cyanoacetateHCID 2723922Sodium ethoxideHCID 86614837HCID 86614837, compound

Product 1

HCID 67273507HCID 67273507, compoundYield 97%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of Precursor A (1-ethoxycarbonylmethyl-3-pyrrolidin-1-yl-methylene-3H-indolium bromide, 4.0 g, 10.8 mmol) and tert-butyl cyanoacetate (15.0 g, 10.8 mmol) in chloroform (100 ml) was added dropwise a solution of sodium ethylate (0.74 g, 10.8 mmol) in dry EtOH (40 ml). The reaction mixture was kept stirring at rt overnight, then diluted with EtOAc (60 ml) and water (30 ml), acidified to pH 3 by adding 1N aqueous HCl. After phase separation, the aqueous phase was extracted twice with EtOAc. The combined organic layers were washed with water and brine, dried over Na2SO4, and the solvent removed under reduced pressure. The residue was dissolved in dichloromethane (20 ml) and treated with trifluoroacetic acid (8.3 ml, 108 mmol) at rt for 4 h. The volatiles were removed under reduced pressure and the residue was azeotoped three times with toluene, then re-crystallized from EtOAc affording subtitle compound (3.15 g) as a yellow solid in 97% yield: tR (LC-2) 1.98 min; ESI-MS(+): m/z 324.35 [M+Na]+ (calcd 298.29 for C16H14N2O4).

Workup

  1. customAfter phase separation
  2. extractionthe aqueous phase was extracted twice with EtOAc
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried over Na2SO4
  5. customthe solvent removed under reduced pressure
  6. dissolutionThe residue was dissolved in dichloromethane (20 ml)
  7. customThe volatiles were removed under reduced pressure
  8. customre-crystallized from EtOAc affording subtitle compound (3.15 g) as a yellow solid in 97% yield
  9. customtR (LC-2) 1.98 min

Sources & evidence

ORD record
ord-eb3e3cb512e845329ef16d8daadfe5f7
Source dataset
uspto-grants-2011_03
Patent number
US07897788B2

Reaction notes

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