Ethyl benzoylacetate → HCID 178487676, compound

HRID 430454Notes

Reaction equation

HRID 430454 reaction equation
[C:1]([CH2:9][C:10]([O:12]CC)=O)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:15][O:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([NH2:23])[CH:18]=1.Cl.O1CCOCC1.C(O)[C@H](O)[C@H]1OC(=O)C(O)=C1O>C1(C)C=CC=CC=1>[OH:12][C:10]1[C:20]2[C:19](=[CH:18][C:17]([O:16][CH3:15])=[CH:22][CH:21]=2)[N:23]=[C:1]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH:9]=1

Participants

6

Reactant 4

HCID 7170Ethyl benzoylacetateHCID 108243-MethoxyanilineHCID 204431481,4-Dioxane hydrochlorideHCID 54670067L-Ascorbic Acid

Product 1

HCID 178487676HCID 178487676, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
280 °C

Procedure

A solution of ethyl benzoylacetate (b) (100.0 g, 0.52 mol), m-anisidine (a) (128.1 g, 1.04 mol) and 4 N HCl/dioxane (5.2 mL) in toluene (1.0 L) was refluxed for 6.25 h in a Dean-Stark apparatus. The cooled toluene solution was successively washed with aqueous 10% HCl (2×300 mL), 1 N NaOH (2×300 mL), H2O (300 mL) and brine (150 mL). The toluene phase was dried (MgSO4), filtered and concentrated under reduced pressure to give a 1.2:1.0 mixture of ester c and amide d (144.6 g, 45%/38% crude yield) as a dark brown oil. The crude oil was heated to 280° C. for 80 min while distilling generated EtOH. The cooled dark solid obtained was triturated with CH2Cl2 (200 mL). The suspension was filtered and the resulting solid washed with CH2Cl2 to give e (22.6 g, 17% from a) as a beige solid: 1H NMR (DMSO-d6) δ 8.00 (d, J=9.0 Hz, 1H), 7.81-7.82 (m, 2H), 7.57-7.59 (m, 3H), 7.20 (d, J=2.2 Hz, 1H), 6.94 (dd, J=9.0, 2.2 Hz, 1H), 6.26 (s, 1H), 3.87 (s, 3H).

Workup

  1. washThe cooled toluene solution was successively washed with aqueous 10% HCl (2×300 mL), 1 N NaOH (2×300 mL), H2O (300 mL) and brine (150 mL)
  2. dry with materialThe toluene phase was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto give
  6. distillationwhile distilling
  7. customThe cooled dark solid obtained
  8. customwas triturated with CH2Cl2 (200 mL)
  9. filtrationThe suspension was filtered
  10. washthe resulting solid washed with CH2Cl2
  11. customto give e (22.6 g, 17% from a) as a beige solid

Sources & evidence

ORD record
ord-f39e6472cd3a4597bb1311017ebe903e
Source dataset
uspto-grants-2001_11
Patent number
US06323180B1

Reaction notes

Loading…