Triethylamine → HCID 9946495, compound

HRID 2099994Notes

Reaction equation

HRID 2099994 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8](/[CH:10]=[CH:11]/[C:12]([NH:14][C:15]3[CH:16]=[C:17](/[CH:21]=[CH:22]/[C:23]([OH:25])=O)[CH:18]=[CH:19][CH:20]=3)=[O:13])=[CH:9][C:4]=2[O:3][CH2:2]1.C(OC(Cl)=O)C(C)C.C(N(CC)CC)C.[OH-:41].[K+].Cl.[NH2:44]O>O1CCCC1.CO>[O:1]1[C:5]2[CH:6]=[CH:7][C:8](/[CH:10]=[CH:11]/[C:12]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17](/[CH:21]=[CH:22]/[C:23]([NH:44][OH:41])=[O:25])[CH:16]=3)=[O:13])=[CH:9][C:4]=2[O:3][CH2:2]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 14797Potassium HydroxideHCID 62365Isobutyl chloroformateHCID 443297Hydroxyamine hydrochlorideHCID 577967883-[3-[[(E)-3-(1,3-Benzodioxol-5-yl)-1-oxo-2-propenyl]amino]phenyl]-(E)-2-propenoic acid

Product 1

HCID 9946495HCID 9946495, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

(Method G5) To a solution of 3-[3-[[(E)-3-(1,3-benzodioxol-5-yl)-1-oxo-2-propenyl]amino]phenyl]-(E)-2-propenoic acid (4a) (0.24 g, 0.71 mmol) in tetrahydrofuran (5.0 ml) at 0° C. temperature iso-butylchloroformate (0.1 ml, 0.80 mmol) and triethylamine (0.12 ml, 0.88 mmol) were added, and the mixture was stirred for 15 min. To a solution of KOH (0.084 g, 1.43 mmol) in methanol (0.40 ml) at 0° C. hydroxylamine hydrochloride (0.10 g, 1.43 mmol) in methanol (1.0 ml) was added and the reaction mixture was stirred for 15 min. The precipitated KCl was removed and the filtrate was added to the first solution. The reaction mixture was stirred at room temperature for 1 hour and then the mixture was partitioned between 1N KH2PO4 and ethyl acetate. The organic layer was washed with water, saturated NaCl, and dried (Na2SO4). The solvent was evaporated and the residue was washed with hot ethyl acetate and hot methanol affording pure title compound (0.13 g, 52%). M.p. 128° C. 1H NMR (DMSO-d6, HMDSO) δ: 6.49 (d, 1H, J=16.0 Hz); 6.67 (d, 1H, J=16.0 Hz); 6.87-7.76 (m, 8 H); 7.98 (br s, 1H); 9.03 (br s, 1H); 10.18 (br s, 1H); 10.80 (br s, 1H). HPLC analysis on Symmetry C18 column: impurities 3.2% (column size 3.9×150 mm; mobile phase acetonitrile−0.1M phosphate buffer (pH 2.5), 50:50; sample concentration 0.5 mg/ml; flow rate 1.0 ml/min; detector UV 254 nm). Anal. Calcd for C19H16N2O5*H2O, %: C, 61.62; H, 4.90; N, 7.56. Found, %: C, 61.93; H, 5.03; N, 7.24.

Workup

  1. stirringthe reaction mixture was stirred for 15 min
  2. customThe precipitated KCl was removed
  3. additionthe filtrate was added to the first solution
  4. stirringThe reaction mixture was stirred at room temperature for 1 hour
  5. customthe mixture was partitioned between 1N KH2PO4 and ethyl acetate
  6. washThe organic layer was washed with water, saturated NaCl
  7. dry with materialdried (Na2SO4)
  8. customThe solvent was evaporated
  9. washthe residue was washed with hot ethyl acetate and hot methanol affording pure title compound (0.13 g, 52%)

Sources & evidence

ORD record
ord-08d66b8bb7544af6b8b8675143fca32c
Source dataset
uspto-grants-2009_08
Patent number
US07569724B2

Reaction notes

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