Hydrochloric Acid → HCID 86722760, compound

HRID 587778Notes

Reaction equation

HRID 587778 reaction equation
Br[C:2]1C=C(/C=C/C(C2C=C(Cl)C(Cl)=C(Cl)C=2)C(F)(F)F)C=[CH:13][C:3]=1[C:4]([NH:6]C(C)(C)C(O)=O)=O.[Br:33][C:34]1[CH:42]=[C:41](/[CH:43]=[CH:44]/[CH:45]([C:50]2[CH:55]=[C:54]([Cl:56])[C:53]([Cl:57])=[C:52]([Cl:58])[CH:51]=2)[C:46]([F:49])([F:48])[F:47])[CH:40]=[CH:39][C:35]=1[C:36](O)=[O:37].S(Cl)(Cl)=O.[C:63]([O-])(O)=O.[Na+].[NH2:68][C:69]([CH3:74])([CH3:73])[C:70](O)=[O:71].Cl>[Br-].C([N+](C)(C)C)CCCCCCCCCCC.C1COCC1.O.ClCCCl>[Br:33][C:34]1[CH:42]=[C:41](/[CH:43]=[CH:44]/[CH:45]([C:50]2[CH:51]=[C:52]([Cl:58])[C:53]([Cl:57])=[C:54]([Cl:56])[CH:55]=2)[C:46]([F:49])([F:47])[F:48])[CH:40]=[CH:39][C:35]=1[C:36]([NH:68][C:69]([CH3:74])([CH3:73])[C:70]([NH:6][CH2:4][C:3]([CH3:13])([CH3:63])[CH3:2])=[O:71])=[O:37]

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 6119Aminoisobutyric acidHCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 86722549(E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)benzoic acidHCID 86722759HCID 86722759, compound

Product 1

HCID 86722760HCID 86722760, compoundYield 85%

Reagents, catalysts & solvents 4

HCID 14249Dodecyltrimethylammonium bromideCatalystHCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

(E)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzamido)-2-methylpropanoic acid: A 25 mL round bottomed flask equipped with a magnetic stir bar and reflux condenser was charged with (E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-en-1-yl)benzoic acid (400 mg, 0.82 mmol) and 1,2-dichloroethane (DCE) (5 mL). Thionyl chloride (0.12 mL, 1.64 mmol) was added neat in one portion and the resulting reaction mixture was heated at reflux for 2 h. After which time, reaction mixture was allowed to cool and concentrated to give the crude acid chloride which was used without further purification. To a solution containing NaHCO3 (68.8 mg, 0.82 mmol), 2-amino-2-methylpropanoic acid (84 mg, 0.82 mmol) and dodecyltrimethylammonium bromide (2.52 mg, 8.19 μmol) in 10 mL of THF was added to the acid chloride in THF (1 mL). The resulting mixture was heated at reflux for 18 h. Reaction mixture was allowed to cool and added to water, made acidic with 0.1N HCl, extracted (3×) with Et2O, washed (1×) with brine, dried over MgSO4, filtered and evaporated to afford the title compound as a light brown foam (400 mg, 85%): 1H NMR (400 MHz, CDCl3) δ 7.60 (d, J=1.6 Hz, 1H), 7.59 (d, J=8.0 Hz, 1H), 7.40 (s, 2H), 7.37 (dd, J=8.1, 1.6 Hz, 1H), 6.63 (s, 1H), 6.53 (d, J=15.9 Hz, 1H), 6.38 (dd, J=15.9, 7.9 Hz, 1H), 4.10 (p, J=8.3 Hz, 1H), 1.73 (s, 6H). This material is used without further purification.

Workup

  1. temperaturereflux condenser
  2. customthe resulting reaction mixture
  3. temperaturewas heated
  4. temperatureat reflux for 2 h
  5. customAfter which time, reaction mixture
  6. temperatureto cool
  7. concentrationconcentrated
  8. customto give the crude acid chloride which
  9. customwas used without further purification
  10. temperatureThe resulting mixture was heated
  11. temperatureat reflux for 18 h
  12. customReaction mixture
  13. temperatureto cool
  14. extractionextracted (3×) with Et2O
  15. washwashed (1×) with brine
  16. dry with materialdried over MgSO4
  17. filtrationfiltered
  18. customevaporated

Sources & evidence

ORD record
ord-705ae8a5b46240239d7eb765232430b6
Source dataset
uspto-grants-2016_01
Patent number
US09226501B2

Reaction notes

Loading…