| Identification | More | [Name]
Isoxepac | [CAS]
55453-87-7 | [Synonyms]
(11-OXO-6,11-DIHYDRODIBENZO[B,E]OXEPIN-2-YL)ACETIC ACID
6,11-DIHYDRO-11-OXO-DIBENZ[B,E]OXEPIN-2-ACETIC ACID
isoxepac
ND4-B2
artil
e)oxepin-2-aceticacid,6,11-dihydro-11-oxo-dibenz(
hp549
DIBENZ[B,E]OXEPIN-2-ACETIC ACID, 6,11-DIOHYDRO-11-OXO
6,11-Hydro-11-Oxo-Dibenz[B,E]Oxepin-2-Acetic Acid
Olapatadine
6,11-DIHYDRO-11-OXO-DIBENZ[B,E]OXEPIN-2-ACETIC ACID(FOR OLOPATADINE)
6,11-dihydro-11-oxo-dibenz[b,e]oxepin-2-acetic acid (Olopatadine)
11-Oxo-6,11-Dihydrobenz(b,e)oxepin-2-Acetic Acid (Isoxepac)
Isoxepac (Dibenz[b,e]oxepin-2-acetic acid, 6,11-dihydro-11-oxo)
6,11-Dihydro-11-oxo-dibenz[b,e]oxepin-2-acetic
2-(11-Oxo-6,11-dihydrodibenzo[b,e]oxepin-2-yl)acetic acid
6,11-Dihydro-11-oxodibenz[b,e]oxepine-2-acetic acid
P-720549
6,11-dihydro-11-oxodibenz[b,e]opepin-2-acetic acid | [EINECS(EC#)]
611-268-9 | [Molecular Formula]
C16H12O4 | [MDL Number]
MFCD00242952 | [Molecular Weight]
268.26 | [MOL File]
55453-87-7.mol |
| Chemical Properties | Back Directory | [Melting point ]
130-132°C | [Boiling point ]
528.2±50.0 °C(Predicted) | [density ]
1.39 g/cm3 | [storage temp. ]
Sealed in dry,Room Temperature | [solubility ]
soluble in Methanol | [form ]
neat | [pka]
4.24±0.10(Predicted) | [color ]
White to Light yellow to Light orange | [Merck ]
14,5237 | [InChI]
InChI=1S/C16H12O4/c17-15(18)8-10-5-6-14-13(7-10)16(19)12-4-2-1-3-11(12)9-20-14/h1-7H,8-9H2,(H,17,18) | [InChIKey]
QFGMXJOBTNZHEL-UHFFFAOYSA-N | [SMILES]
O1CC2=CC=CC=C2C(=O)C2=CC(CC(O)=O)=CC=C12 | [CAS DataBase Reference]
55453-87-7(CAS DataBase Reference) |
| Safety Data | Back Directory | [Hazard Codes ]
T | [Risk Statements ]
25-62 | [Safety Statements ]
36/37-45 | [RIDADR ]
UN 2811 6.1 / PGIII | [RTECS ]
HQ4110000 | [HazardClass ]
6.1 | [PackingGroup ]
III | [HS Code ]
2932996560 | [Toxicity]
LD50 orally in rats: 199 mg/kg (Ueno) |
| Hazard Information | Back Directory | [Chemical Properties]
Beige Solid | [Uses]
Non-steroidal anti-inflammatory with analgesic and antipyretic activity | [Definition]
ChEBI: Isoxepac is a dibenzooxazepine. | [Preparation]
Isoxic acid is an important intermediate in the synthesis of the new preferred anti-allergic drug, olopatadine hydrochloride, preparation method of isoxepac:
(1), condensation: prepare p-hydroxyphenylaceticacid 8-12 part, phthalide 6-12 part, sodium methylate 8-12 part by weight; Dissolve with DMAC and to add said sodium methylate behind said p-hydroxyphenylaceticacid and the phthalide; Be that 0.1-10Pa is heated to 80-170 ℃ of reaction 3-10h at pressure then; Regulate the pH value to 1-5,4-(2-carboxyl benzyloxy) toluylic acid is separated out in crystallization;
(2), cyclization: with Glacial acetic acid min. 99.5 dissolving step (1) gained 4-(2-carboxyl benzyloxy) toluylic acid, adding 3-52 weight part polyphosphoric acid again, is that 0.1-10Pa is heated to 30-100 ℃ of reaction 3-12h at pressure, and crystallisation by cooling gets the Isoxepac bullion then;
(3), purify: behind the said Isoxepac bullion of acetic acid ethyl dissolution, refining decolouring gets the Isoxepac product.
https://patents.google.com/patent/CN102838582A/en | [Brand name]
Artil(Hoechst-Roussel)
. | [Synthesis]
General procedure for the synthesis of 2-(11-oxo-6,11-dihydrodibenzo[b,e]oxazepin-2-yl)acetic acid from 2-[(4-carboxymethylphenoxy)methyl]benzoic acid: 2-[(4-carboxymethylphenoxy)methyl]benzoic acid (total amount) obtained in Step 4 was added to a 500 mL four-necked flask with 200 mL of chlorobenzene, 75.0 g ( 0.3753 mol) trifluoroacetic anhydride, and the reaction was stirred at about 20°C for 4 hours. Subsequently, 2.3 g (0.0162 mol) of boron trifluoride-ether complex was slowly added dropwise over 10 minutes at -10 to 0 °C and stirring was continued for 30 minutes. After completion of the reaction, the aqueous phase was separated and the organic layer was washed with 200 mL of water. The washed organic layer was added to 300 mL of aqueous solution with 7.2 g of sodium hydroxide dissolved in it and stirred for 30 minutes, and the aqueous phase was again separated. To the aqueous phase, 2.0 g of activated carbon was added and stirred for 30 minutes, then the activated carbon was removed by filtration through a Brinell funnel and the activated carbon was washed with 10 mL of water. The filtrate was combined with the wash solution, the temperature was maintained at about 40 °C, and a mixture consisting of 11.3 g (0.1876 mol) acetic acid with 50 mL of water was added dropwise over 30 minutes. After the dropwise addition, the mixture was cooled to 0 to 10 °C and the crystals were collected by filtration through a Brinell funnel and washed with 200 mL of water. The resulting crystals were dried under reduced pressure to afford 42.0 g of the target product 2-(11-oxo-6,11-dihydrodibenzo[b,e]oxazepin-2-yl)acetic acid in 96.4% yield (based on 2-[(4-carboxymethylphenoxy)methyl]benzoic acid) and 99.9% purity by HPLC.HPLC conditions:The chromatographic column was Inertsil ODS-5 μm ( 4.6 mm ID×15 cm); mobile phase was 0.02% aqueous trifluoroacetic acid/acetonitrile=5/5→3/7 (30 min); detection wavelength was UV 254 nm. Physical property data: 1H NMR (400 MHz, DMSO-d6) δ 3.63 (s, 2H), 5.30 (s, 2H), 7.07 (d, J=8.0 Hz, 2H) , 7.48 (t, J=3.6 Hz, 1H), 7.55 (dd, J=7.9 Hz, 2H), 7.67 (t, J=7.6 Hz, 1H), 7.78 (d, J=7.6 Hz, 1H), 7.97 (d, J=2.0 Hz, 1H). | [storage]
Store at -20°C | [References]
[1] Patent: EP2072507, 2009, A1. Location in patent: Page/Page column 10-11
[2] Patent: US2007/232814, 2007, A1. Location in patent: Page/Page column 23-24
[3] Patent: CN104262318, 2016, B. Location in patent: Paragraph 0055; 0056
[4] Journal of Medicinal Chemistry, 1996, vol. 39, # 1, p. 246 - 252
[5] Patent: US4585788, 1986, A |
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