prop-2-enoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The obtained olopatadine hydrochloride was mixed with about 2 mL of ethyl acetate. The mixture was subjected to ultrasonication in disposable cup for about 30 seconds in order to dissolve or disperse olopatadine hydrochloride, and fully mixed with isopropyl myristate. Acrylic pressure sensitive adhesive 3.7125 g (PE-300; acrylate copolymer; solid content of 40% by weight (ethyl acetate/toluene mixed solvent): 1.485 g; Nippon Carbide Industries Co., Ltd.) and crosslinking agent 0.015 g (CK401; metal chelate; solid content of about 10% by weight (toluene solvent): 0.0015 g; Nippon Carbide Industries Co., Ltd.) were sequentially added to the mixture. The mixture was fully mixed and degassed. The mixture was spread over release liner using metering knife or baker applicator, and stood until the organic solvent was completely evaporated. Subsequently, support was laid over the release liner and compressed using roller, and subjected to crosslinking in temperature controlled bath for 8 to 12 hours at about 40° C. to give adhesive preparation comprising olopatadine hydrochloride. The mixture was subjected to ultrasonication in disposable cup for about 30 seconds in order to dissolve were sequentially added to the mixture The mixture was fully mixed degassed was completely evaporated for 8 to 12 hours at about 40° C. to give adhesive preparation

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Terpolymer derivatives having either acrylate or methacrylate units and benzophenone moieties substituted on the isobutylene/para-methylstyrene/para-bromomethylstyrene were then prepared. A 5000 ml glass-jacketed reaction vessel fitted with an overhead stirrer, a hose connector and septum was purged with nitrogen. At room temperature under nitrogen, the vessel was charged with toluene (2500 ml) and 450 g of the base isobutylenelparamethylstyrene/para-bromomethylstyrene terpolymer above comprising 2.4 total mole percent para-methylstyrene, including 1.10 mole percent para-bromomethylstyrene, and having a Mooney viscosity of 32 (1+8 min., 125° C.). The base terpolymer was dissolved by stirring at room temperature overnight. A tetrabutylammonium salt of acrylic acid (or methacrylic acid) was prepared in a second flask by charging 101.3 ml tetrabutylammonium hydroxide (1.0M in methanol) and 7.3 ml acrylic acid (7.0 ml methacrylic acid) and 4 g of 4-hydroxybenzophenone and 30 ml of methanol to the flask and stirring at room temperature to give a water-white clear solution. This solution was then added to the flask containing the dissolved base terpolymer, at a circulating bath temperature of 83° C. After 45 minutes, the bath temperature was raised to 95° C. and let to run for 7.5 h. Then the bath temperature was lowered to 70° C., and after a 2.5 h period, the reaction was let to cool. The yellowish viscous solution was quenched and washed with 10 ml HCl in 1000 ml deionized water, and subsequently washed with H2O/IPA (70:30) 5 to 6 times. The polymer was isolated by precipitation into 0.1% BHT in isopropanol (IPA) and dried in vacuo for 48 h at 1 mm Hg and 80° C. were then prepared A 5000 ml glass-jacketed reaction vessel fitted with an overhead stirrer a hose connector and septum was purged with nitrogen At room temperature under nitrogen, the vessel was charged with toluene (2500 ml) and 450 g of the base isobutylenelparamethylstyrene/para-bromomethylstyrene terpolymer a Mooney viscosity of 32 (1+8 min., 125° C.) The base terpolymer was dissolved stirring at room temperature This solution was then added to the flask containing the dissolved base terpolymer temperature of 83° C After 45 minutes the bath temperature was raised to 95° C. to run for 7.5 h was lowered to 70° C. after a 2.5 h period to cool The yellowish viscous solution was quenched washed with 10 ml HCl in 1000 ml subsequently washed with H2O/IPA (70:30) 5 to 6 times The polymer was isolated by precipitation into 0.1% BHT in isopropanol (IPA) dried in vacuo for 48 h at 1 mm Hg and 80° C.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: As a compound having at least one addition polymerizable ethylenically unsaturated group and a boiling point of 100° C. or more under normal pressure, there can be exemplified a monofunctional acrylate and methacrylate such as polyethylene glycol mono(meth)acrylate, polypropylene glycol mono(meth)acrylate, and phenoxyethyl(meth)acrylate; compounds obtained by the addition of ethylene oxide or propylene oxide to polyfunctional alcohol such as polyethylene glycol di(meth)acrylate, trimethylolethane tri(meth)acrylate, neopentyl glycol di(meth)acrylate, pentaerythritol tri(meth)acrylate, pentaerythritol tetra(meth)acrylate, dipentaerythritol hexa(meth)acrylate, hexanediol (meth)acrylate, trimethylolpropane, tri(acryloyloxypropyl) ether, tri(acryloyloxyethyl)isocyanurate, glycerin, and trimethylolethane, and then having (meth)acrylated; urethane acrylates as disclosed in JP-B-48-41708, JP-B-50-6034, and JP-A-51-37193; polyester acrylates as disclosed in JP-A-48-64183, JP-B-49-43191, and JP-B-52-30490; and polyfunctional acrylates and methacrylates such as epoxy acrylates which are reaction products of epoxy resins and (meth)acrylic acids. Further, photocurable monomers and oligomers described in Nihon Setchaku Kyokai Shi (Bulletin of Japan Adhesion Association), Vol. 20, No. 7, pp. 300 to 308 can also be used. As a compound having at least one addition polymerizable ethylenically unsaturated group

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-fluoro-2-methylaniline (about 1 g) in chloroform (5 ml) was added dropwise to a solution of ethyl 3-ethoxy-2-(2',5'-difluoro-3'-methyl-4'-nitrobenzoyl)acrylate (2.0 g) in chloroform (10 ml) at room temperature (while confirming the disappearance of the acrylate by tlc). After the mixture was stirred for 10 minutes, the solvent and the like were distilled off. Potassium carbonate (800 mg) was added to a solution of the whole amount of the residue in dimethylformamide (3 ml), and the mixture was stirred at 110° C. for 20 minutes. Chloroform and water were added to the reaction mixture to collect an organic layer. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off. Ethanol was added to the residue to disperse it therein, and filtration was conducted to obtain the title compound (1.1 g) as a pale yellow powder. the solvent and the like were distilled off Potassium carbonate (800 mg) was added to a solution of the whole amount of the residue in dimethylformamide (3 ml) the mixture was stirred at 110° C. for 20 minutes Chloroform and water were added to the reaction mixture to collect an organic layer After the organic layer was dried over anhydrous magnesium sulfate the solvent was distilled off Ethanol was added to the residue to disperse it filtration

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of (DHQ)2 -PHAL (0.11 g, 0.14 mmol, 5 mol %) in 20 mL of acetonitrile and 20 mL of water, in any convenient-sized glass vessel or vial, was added desired acrylate or methacrylates entries 1-10 (all commercially available from Aldrich, FIG. 16 and FIG. 17, 2.8 mmol), Chloramine-T trihydrate (2.42 g, 8.4 mmol, 3 eq) and K2OsO2 (OH)4 (41.6 mg, 0.112 mmol, 4 mol %). As the reaction proceeded to completion over the course of about one and half hours at room temperature, the color of the solution changed from yellow to pale green, then deep green and finally back to yellow. After addition of aqueous sodium sulfite (1.0 g in 15 mL H2O), the phases were separated, and the aqueous phase extracted with ethyl acetate (3×15 mL). The combined organic extracts were washed with brine, dried over MgSO4 and the solvent concentrated to give the crude product, which also contains the p-toluenesulfonamide by-product produced upon the reduction of the excess Chloramine-T. Purification provides compounds as shown in FIG. 16, entries 1-10 with the indicated yields and conditions. NOTE: Replacement of the 3 eq of Chloramine-T with 1.5 eq of Chloramine-T and 1.5 eq of Et4NOAc gives comparable results and reduces the amount of p-toluenesulfonamide by-product formed. This can greatly simplify product isolation, especially in cases where the product and the toluenesulfonamide have similar chromatographic mobilities. ##STR17## proceeded to completion over the course of about one and half hours at room temperature the phases were separated the aqueous phase extracted with ethyl acetate (3×15 mL) The combined organic extracts were washed with brine dried over MgSO4 the solvent concentrated to give the crude product, which