Toluene → 2-(2-methoxy-2-oxoethyl)-4-phenyl-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid

HRID 1007144Notes

Reaction equation

HRID 1007144 reaction equation
[CH3:1][O:2][C:3](=[O:22])[CH2:4][CH:5]1[CH2:10][NH:9][C:8]2[CH:11]=[C:12]([C:15]([O:17]C(C)(C)C)=[O:16])[CH:13]=[CH:14][C:7]=2[O:6]1.[C:23]1(C)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>>[CH3:1][O:2][C:3](=[O:22])[CH2:4][CH:5]1[CH2:10][N:9]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:8]2[CH:11]=[C:12]([C:15]([OH:17])=[O:16])[CH:13]=[CH:14][C:7]=2[O:6]1

Participants

4

Reactant 3

HCID 1140TolueneHCID 6101p-Toluenesulfonic acidHCID 22667860tert-butyl 2-(2-methoxy-2-oxoethyl)-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate

Product 1

HCID 226678362-(2-methoxy-2-oxoethyl)-4-phenyl-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acidYield 52%

Procedure

To a stirred suspension of tert-butyl 2-(2-methoxy-2-oxoethyl)-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate (5.3 g, 17.3 mmol) in toluene (50 mL) 1,4-cyclohexandione (2.8 g, 25 mmol) and p-toluenesulfonic acid (1 g) were added. The resulting solution was stirred at reflux for 4 hours, using a condenser equipped with a Dean-Stark apparatus. The reaction mixture was concentrated in vacuo. The remaining oil was purified by flash chromatography on silica gel column eluting with ethyl acetate to give 2-(2-methoxy-2-oxoethyl)-4-phenyl-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid (2.9 g, 52%) as a white solid.

Workup

  1. additionwere added
  2. temperatureat reflux for 4 hours
  3. customequipped with a Dean-Stark apparatus
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customThe remaining oil was purified by flash chromatography on silica gel column
  6. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-fe5bb9f114dd439b8d12540ac889d02b
Source dataset
uspto-grants-2004_09
Patent number
US06794385B2

Reaction notes

Loading…