Water → Isoxepac

HRID 2247132Notes

Reaction equation

HRID 2247132 reaction equation
[C:1]([C:4]1[CH:21]=[CH:20][CH:19]=[CH:18][C:5]=1[CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][C:15]([OH:17])=[O:16])=[CH:10][CH:9]=1)([OH:3])=O.FC(F)(F)C(OC(=O)C(F)(F)F)=O.O>C1(C)C=CC=CC=1.FC(F)(F)S(O)(=O)=O>[O:3]=[C:1]1[C:4]2[CH:21]=[CH:20][CH:19]=[CH:18][C:5]=2[CH2:6][O:7][C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C:15]([OH:17])=[O:16])=[CH:10][C:9]1=2

Participants

6

Reactant 3

HCID 962WaterHCID 9845Trifluoroacetic anhydride2×HCID 122923092-((4-Carboxymethylphenoxy)methyl)benzoic acid

Product 1

HCID 41448IsoxepacYield 73.1%

Reagents, catalysts & solvents 2

HCID 62406Trifluoromethanesulfonic acidCatalystHCID 1140TolueneSolvent

Conditions

Temperature
75 °C

Procedure

To a suspension of 4-(2-carboxybenzyloxy)phenylacetic acid (Olo-IM1) (300.09 g, 1.04 mol; assay: 99.0%) and trifluoromethane sulfonic acid (4.77 g, 0.03 mol; assay: 98.0%) in toluene (1122 g) was added slowly trifluoroacetic anhydride (255.18 g, 1.20 mol; assay: 99.0%) at 20-35° C. The brown solution was stirred after complete addition of trifluoroacetic anhydride for 1 hour at 20-25° C. and the mixture was then hydrolyzed with water (99.0 g). Afterwards, the mixture was distilled under normal pressure until the steam temperature was 105-110° C. (1191 g two-phase distillate). The residue was diluted with toluene (261 g) and the suspension was heated to reflux. The dark solution was then cooled to 75° C. and seeded with crystals of 6,11-dihydro-11-oxo-dibenz[b,e]oxepin-2-acetic acid (Olo-IM2). The suspension was stirred after cooling to 20-25° C. for additional 1-2 hours at this temperature. The product was filtered off, washed with cyclohexane (600 g) and water (390 g) and dried under vacuum (20 h, 50° C.) to give 6,11-dihydro-11-oxo-dibenz[b,e]oxepin-2-acetic acid (Olo-IM2) (yield: 203.21 g, 0.76 mol, 73.0%; HPLC assay >99.5%, HPLC purity: 99.62%). This product was then recrystallized from a mixture of cyclohexane (700 g) and toluene (1892 g). After filtration the wet product was washed with cyclohexane (466 g) and dried under vacuum (15 h, 70° C.) to give slightly gray colored 6,11-dihydro-11-oxo-dibenz[b,e]oxepin-2-acetic acid (Olo-IM2) (yield: 198.4 g, 0.74 mol, 97.6%; HPLC assay >99.5%, HPLC purity: 99.90%; overall yield: 71.3%).

Workup

  1. distillationAfterwards, the mixture was distilled under normal pressure until the steam temperature
  2. customwas 105-110° C.
  3. additionThe residue was diluted with toluene (261 g)
  4. temperaturethe suspension was heated to reflux
  5. stirringThe suspension was stirred
  6. temperatureafter cooling to 20-25° C. for additional 1-2 hours at this temperature
  7. filtrationThe product was filtered off
  8. washwashed with cyclohexane (600 g) and water (390 g)
  9. customdried under vacuum (20 h, 50° C.)

Sources & evidence

ORD record
ord-b5ec950db0044ea492d043035d9c7fc0
Source dataset
uspto-grants-2010_03
Patent number
US07687646B2

Reaction notes

Loading…