1,2-Dichloroethane → HCID 23557342, compound

HRID 1635893Notes

Reaction equation

HRID 1635893 reaction equation
CO[C:3](=[O:17])/[CH:4]=[CH:5]/[CH:6]=[CH:7]/[CH2:8][CH2:9][C:10]([O:12][C:13](C)(C)C)=[O:11].C(O)(C(F)(F)F)=O.[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(Cl)CCl>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCOC(C)=O>[CH3:13][O:12][C:10](=[O:11])/[CH:9]=[CH:8]/[CH:7]=[CH:6]/[CH2:5][CH2:4][C:3](=[O:17])[NH:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 6115AnilineHCID 6422Trifluoroacetic acidHCID 23557344HCID 23557344, compound

Product 1

HCID 23557342HCID 23557342, compoundYield 58%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of diester 43 (1.00 g, 4.61 mmol) in CH2Cl2 (40 mL) was added TFA (4.0 mL) and let react for 6 h. The mixture was concentrated under reduced pressure to remove volatiles. A white solid consisting of the crude acid (710 mg, 3.85 mmol) remained. This acid (400 mg, 2.17 mmol) was dissolved in CH2Cl2 (20 mL) and to this stirred solution were added DMAP (13 mg), aniline (218 μL, 2.39 mmol), and EDC (500 mg, 2.61 mmol). After 1.5 h, the mixture was diluted with EtOAc and washed with H2O. The layers were separated, and the aqueous extracted with EtOAc (3×15 mL). The organic portions were combined and washed with HCl (1 N, 1×5 mL) and brine, dried over MgSO4, and filtered. Concentration under reduced pressure left a brown solid. This was dissolved in a minimum of CH2Cl2, then passed through a plug of silica gel (20-30% EtOAc/hexanes, 200 mL) to remove baseline impurities. The eluent was concentrated to a light brown oil which was taken up in a small amount of CH2Cl2 and from which crystals were precipitated up6n the addition of hexanes/diethyl ether. The mother liquor was drawn off, the crystals rinsed with ether, and the liquid fraction concentrated and this procedure repeated several times to ultimately give 44 as off-white crystals (324 mg, 1.25 mmol, 58%). TLC Rf 0.44 (50% EtOAc/hexanes); 1H-NMR (400 MHz, CDCl3) δ 7.47 (d, 1H), 7.30 (t, 2H), 7.24 (m, 1H), 7.09 (t, 1H), 6.24 (dd, 1H), 6.14 (m, 1H), 5.81 (d, 1H), 3.72 (s, 3H), 2.60 (m, 2H), 2.47 (t, 2H).

Workup

  1. customlet react for 6 h
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customto remove volatiles
  4. washwashed with H2O
  5. customThe layers were separated
  6. extractionthe aqueous extracted with EtOAc (3×15 mL)
  7. washwashed with HCl (1 N, 1×5 mL) and brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationConcentration under reduced pressure
  11. waitleft a brown solid
  12. dissolutionThis was dissolved in a minimum of CH2Cl2
  13. customto remove baseline impurities
  14. concentrationThe eluent was concentrated to a light brown oil which
  15. customwere precipitated up6n the addition of hexanes/diethyl ether
  16. washthe crystals rinsed with ether
  17. concentrationthe liquid fraction concentrated

Sources & evidence

ORD record
ord-df8952ee78b74a278789b97a86999ce3
Source dataset
uspto-grants-2003_01
Patent number
US06511990B1

Reaction notes

Loading…