1,2-Dichloroethane → HCID 9882812, compound

HRID 1635902Notes

Reaction equation

HRID 1635902 reaction equation
CO[C:3](=[O:16])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10](=[O:15])[C:11]([F:14])([F:13])[F:12].O[Li].O.Cl.C(Cl)CCl.[NH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C1COCC1.O.CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:26]1([NH:25][C:3](=[O:16])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10](=[O:15])[C:11]([F:12])([F:13])[F:14])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

10

Reactant 5

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 6115AnilineHCID 168937Lithium hydroxide, monohydrateHCID 23557343HCID 23557343, compound

Product 1

HCID 9882812HCID 9882812, compoundYield 65%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ester 71 (300 mg, 1.25 mmol) in THF (18 mL) was added a solution of LiOH.H2O (262 mg, 6.24 mmol) in H2O (6 mL) and the suspension was stirred overnight. The mixture was then acidified with HCl (1 N) to pH 2 and then extracted with EtOAc (3×15 mL). The extracts were combined, washed with brine, dried over MgSO4, and filtered. Concentration under reduced pressure left a white solid (211 mg, 0.93 mmol, 75%). To a solution of this acid (109 mg, 0.48 mmol), EDC (111 mg, 0.58 mmol), and DMAP (5 mg) in CH2Cl2 (5 mL) was added aniline (49 μL, 0.53 mmol) and the reaction allowed to proceed overnight. The solution was partitioned between H2O (5 mL) and EtOAc (10 mL). The layers were separated, and the aqueous phase extracted with EtOAc (3×5 mL). The organic portions were combined, washed with brine, dried over MgSO4, and filtered. Evaporation under reduced pressure left a solid which was purified by preparative TLC (30% EtOAc/hexanes) with isolation of the least polar band by EtOAc extraction. The extract was concentrated to give 72 as a yellowish solid (92 mg, 0.31 mmol, 65%). TLC Rf 0.48 (50% EtOAc/hexanes); 1H-NMR (400 MHz, CDCl3) δ 7.51 (d, 2H), 7.32 (t, 2H), 7.10 (t, 1H), 2.72 (t, 2H), 2.36 (t, 2H), 1.72 (m, 4H), 1.40 (m, 4H); 19F NMR (? MHz, CDCl3) −78.40 (s, 3F); MS (APCI+) calcd for C15H19F3NO2 301, found 325 [M+Na]+.

Workup

  1. extractionextracted with EtOAc (3×15 mL)
  2. washwashed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationConcentration under reduced pressure
  6. waitto proceed overnight
  7. customThe solution was partitioned between H2O (5 mL) and EtOAc (10 mL)
  8. customThe layers were separated
  9. extractionthe aqueous phase extracted with EtOAc (3×5 mL)
  10. washwashed with brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. customEvaporation under reduced pressure
  14. waitleft a solid which
  15. customwas purified by preparative TLC (30% EtOAc/hexanes) with isolation of the least polar band by EtOAc extraction
  16. concentrationThe extract was concentrated

Sources & evidence

ORD record
ord-8394e7c925f84983ab10c8b0f18a0c0e
Source dataset
uspto-grants-2003_01
Patent number
US06511990B1

Reaction notes

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