Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]1([C:7]2[CH:8]=[CH:9][C:10]3[O:14][C:13](B(O)O)=[CH:12][C:11]=3[CH:18]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:20]1[CH:27]=[CH:26][C:23]([CH:24]=[O:25])=[CH:22][CH:21]=1.C(N(CC)CC)C>C(O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[N:1]1([C:7]2[CH:8]=[CH:9][C:10]3[O:14][C:13]([C:20]4[CH:27]=[CH:26][C:23]([CH:24]=[O:25])=[CH:22][CH:21]=4)=[CH:12][C:11]=3[CH:18]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=Cc1ccc(Br)cc1
Reactant: OB(O)c1cc2cc(N3CCCCC3)ccc2o1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CCO
Solvent: CCN(CC)CC
Product: O=Cc1ccc(-c2cc3cc(N4CCCCC4)ccc3o2)cc1
Yield: 30.8 %

Procedure:
A mixture of 5-(piperidin-1-yl)benzofuran-2-ylboronic acid (90 mg, 0.367 mmol), 4-bromobenzaldehyde (62 mg, 0.330 mmol), triethylamine (1.0 mL, 7.3 mmol) and bis(triphenylphosphine)palladium(II) chloride (12.8 mg, 0.02 mmol) in ethanol (9 mL) was irradiated in a microwave instrument at 100° C. for 20 min. The reaction mixture was cooled, and the solvent was removed. The residue was purification by silica gel chromatography on ISCO system yielding the title compound (31 mg, 28% yield). ESI-MS: 306.4 (M+H)+, 1H NMR (400 MHz, CDCl3) δ 10.02 (s, 1H), 7.95 (dd, 4H), 7.42 (d, 1H), 7.11 (m, 2H), 7.07 (dd, 1H), 3.13 (t, 4H), 1.78-1.74 (m, 4H), 1.62-1.56 (m, 2H).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([OH:9])=[C:4]([Cl:10])[CH:3]=1.Cl[C:12]1[S:13][C:14]2[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:15]=2[N:16]=1.C([O-])([O-])=O.[K+].[K+].Cl>CS(C)=O.O>[Cl:8][C:6]1[CH:7]=[C:2]([NH2:1])[CH:3]=[C:4]([Cl:10])[C:5]=1[O:9][C:12]1[S:13][C:14]2[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:15]=2[N:16]=1
Reactant: Clc1ccc2nc(Cl)sc2c1
Reactant: Nc1cc(Cl)c(O)c(Cl)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: Nc1cc(Cl)c(Oc2nc3ccc(Cl)cc3s2)c(Cl)c1
Temperature: 160 °C
Yield: 49.3 %

Procedure:
To the solution of 4-amino-2,6-dichloro phenol (6 g, 26.5 mmol) and 2,6-dichlorobenzothiazole (101) (6 g, 29.4 mmol, 1.1 equiv.) in DMSO (25 mL), was added K2CO3 (11 g, 80 mmol, 3.0 equiv.). The mixture was stirred and heated to 160° C. After 5.5 h water (20 mL) was added to the reaction mixture, which was neutralized with 2N HCl, and was extracted with AcOEt three times. And the organic layer was washed with brine and was dried over anhydrous MgSO4, and then concentrated. Crude residue was purified by column chromatography (CHCl3/acetone=9/1, 180 g of silica gel) to afford 3,5-dichloro-4-(6-chloro-benzothiazol-2-yloxy)-phenylamine (102) as a black solid (4.52 g, 49%). 1H NMR (300 MHz, DMSO-d6) δ 5.86 (2H, br s), 6.74 (2H, s), 7.48 (1H, dd, J=2.1, 5.7 Hz), 7.70 (1H, d, 8.7 Hz), 8.10 (1H, d, 2.1 Hz).
Reaction SMILES: C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:13]([O:20][C:21]([NH:23][CH2:24][C:25]([OH:27])=O)=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(=O)=O.[CH3:31][O:32][C:33](=[O:43])[C@H:34]([CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[NH2:35].O>O1CCCC1>[CH3:31][O:32][C:33](=[O:43])[C@H:34]([CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[NH:35][C:25](=[O:27])[CH2:24][NH:23][C:21]([O:20][CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[O:22]
Reactant: O=C(O)CNC(=O)OCc1ccccc1
Reactant: COC(=O)[C@@H](N)Cc1ccccc1
Agent: O=C(n1ccnc1)n1ccnc1
Agent: O=C=O
Solvent: O
Solvent: C1CCOC1
Product: COC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)OCc1ccccc1
Reaction time: 2 h

Procedure:
Solid carbonyldiimidazole (79.10 g, 0.488 mol) was added to a room temperature solution of N-benzyloxycarbonyl-glycine (117.11 g, 0.560 mol) in anhydrous tetrahydrofuran (THF, 600 mL). The resulting solution was stirred for 45 minutes until CO2 evolution had ceased. A solution of L-phenylalanine methyl ester (79.65 g, 0.444 mol) in anhydrous THF (~200 mL) was then added. The reaction temperature was maintained below 40° C. by application of a water bath to the exterior of the reaction vessel. After two hours, a small portion of water (1.5 mL, ~0.08 mol) was added to the reaction mixture to hydrolyze any remaining acylimidazolides and the resulting solution was left to stir overnight. The reaction mixture was concentrated in vacuo and the residual oil was dissolved in ethyl acetate (~1 L). This ethyl acetate solution was extracted with 1 N HCI (2×300 mL--the first aqueous extract was acidified a pH of 1 by addition of 6 N HCl), water (300 mL), saturated aqueous sodium carbonate (300 mL), half-saturated aqueous sodium carbonate (250 mL), and brine (250 mL). The organic phase was dried by filtration through magnesium sulfate and sodium sulfate and concentrated in vacuo to constant weight. Field desorption mass spectrometry (FDMS) of the resulting oil (160.88 g, ~0.434 mol, 98%) indicated the presence of a single component (M+=370). This material was not further purified, but was instead converted directly into cyclo-glycyl-L-phenylalanine (8) by catalytic hydrogenation (vide infra).
Reaction SMILES: [CH2:1]([NH:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]=[CH:8][C:7]=1[N+:16]([O-])=O)[CH:2]([CH3:4])[CH3:3]>C1(C)C=CC=CC=1.[Pt]>[NH2:16][C:7]1[CH:8]=[N:9][C:10]2[C:15]([C:6]=1[NH:5][CH2:1][CH:2]([CH3:4])[CH3:3])=[CH:14][CH:13]=[CH:12][CH:11]=2
Reactant: CC(C)CNc1c([N+](=O)[O-])cnc2ccccc12
Agent: [Pt]
Solvent: Cc1ccccc1
Product: CC(C)CNc1c(N)cnc2ccccc12
Yield: 100.6 %

Procedure:
4-isobutylamino-3-nitroquinoline (31.5 g, 0.1284 moles) from Step (A) above, was dissolved in 300 ml of toluene, and 1 g of 5% platinum on carbon was added thereto. The resulting mixture was hydrogenated on a Parr apparatus for one and one-half hours. The mixture was then heated and filtered. Toluene was removed from the filtrate by rotary evaporation to provide 27.8 g of crude 3-amino-4-(isobutylamino)quinoline. Recrystallization twice from ethyl acetate/hexane provided 18.8 g of purified product, m.p. 98°-100° C. Analysis: Calculated for C13H17N3 : %C, 72.5; %H, 8.0; %N, 19.5; Found: %C, 73.2; %H, 7.8; %N, 19.7.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([CH:11]1[CH2:15][CH2:14][N:13]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:12]1)=O.Cl.C([O-])(=[O:26])C.[NH4+:28]>C(O)C.O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([CH:11]1[CH2:15][CH2:14][N:13]([CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:12]1)=[N:28][OH:26]
Reactant: O=C(c1ccc(F)cc1F)C1CCN(Cc2ccccc2)C1
Reactant: [NH4+]
Reactant: CC(=O)[O-]
Agent: Cl
Solvent: CCO
Solvent: O
Product: ON=C(c1ccc(F)cc1F)C1CCN(Cc2ccccc2)C1
Temperature: 25 °C
Reaction time: 24 h
Yield: 52 %

Procedure:
To the compound (2,4-difluorophenyl)[1-(phenylmethyl)-3-pyrrolidinyl]methanone (22 g) in 95% ethanol (350 ml) and water (100 ml) was added NH2O.HCl (10.1 g) and ammonium acetate (12.7 g, 2.1 eq). The resulting mixture was refluxed for 3.5 hours. The mixture was then allowed to stir at room temperature for 24 hour. The reaction mixture was concentrated to remove ethanol, poured into water (500 ml), and extracted with dichloromethane (500 ml). This was followed by washing with water, brine, and drying over magnesium sulfate. The product was concentrated to an oil and purified by column chromatography to yield 12 g of (2,4-difluorophenyl)[1-(phenylmethyl)-3-pyrrolidinyl]methanone oxime.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[CH3:9].C(NC(C)C)(C)C.[CH3:17][O:18][CH2:19]Cl.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:17][O:18][CH3:19])=[CH:4][C:3]=1[CH3:9]
Reactant: COCCl
Reactant: Cc1cc(O)ccc1Br
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Solvent: ClCCl
Solvent: CC(C)NC(C)C
Product: COCOc1ccc(Br)c(C)c1
Temperature: 25 °C
Reaction time: 120 h

Procedure:
To a solution of 4-bromo-3-methylphenol (14 g) and N,N-diisopropylamine (39.1 mL) in dichloromethane (150 mL) was added chloromethyl methyl ether (11.4 mL) under ice-cooling, and the mixture was stirred at room temperature for 5 days. The reaction mixture was poured into a saturated aqueous citric acid solution, and the resulting mixture was extracted with diethyl ether. The extract was washed with water, 1 mol/L aqueous sodium hydroxide solution, water and brine successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 4-bromo-3-methyl-1-(methoxymethoxy)benzene (16.7 g). This material was dissolved in tetrahydrofuran (250 mL). To the solution was added n-butyl lithium (2.64 mol/L n-hexane solution, 32.7 mL) at −78° C. under an argon atmosphere, and the mixture was stirred at the same temperature for 15 minutes. To the reaction mixture was added N,N-dimethylformamide (16.6 mL), and the mixture was stirred under ice-cooling for 1 hour. The reaction mixture was poured into a saturated aqueous ammonium chloride solution, and the resulting mixture was extracted with diethyl ether. The extract was washed with a saturated aqueous sodium hydrogen carbonate solution and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 2-methyl-4-(methoxymethoxy)benzaldehyde (12.9 g). This material was dissolved in tetrahydrofuran (70 mL)-methanol (10 mL). To the solution was added concentrated hydrochloric acid (6 mL), and the mixture was stirred at 50° C. for 1.5 hours. The reaction mixture was poured into a saturated aqueous sodium hydrogen carbonate solution, and the resulting mixture was extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate (30 mL) with heating at 60° C. n-Hexane (100 mL) was added to the solution gently, and the mixture was stirred at the same temperature for 10 minutes. The mixture was cooled to room temperature. n-Hexane (170 mL) was added to the mixture, and the resulting mixture was stirred overnight. The precipitated crystals were collected by filtration, and washed with n-hexane and dried under reduced pressure to give the title compound (5.6 g).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]=[N:11][C:12]1[CH:17]=[C:16]([C:18]([CH2:21][CH3:22])([CH3:20])[CH3:19])[CH:15]=[C:14]([C:23]([CH2:26][CH3:27])([CH3:25])[CH3:24])[C:13]=1[OH:28])([O-])=O.C(N)(C)(C)C.[PH2](O)=O>[Pd].CO>[OH:28][C:13]1[C:14]([C:23]([CH2:26][CH3:27])([CH3:25])[CH3:24])=[CH:15][C:16]([C:18]([CH2:21][CH3:22])([CH3:20])[CH3:19])=[CH:17][C:12]=1[N:11]1[N:10]=[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]2=[N:1]1
Reactant: CCC(C)(C)c1cc(N=Nc2ccccc2[N+](=O)[O-])c(O)c(C(C)(C)CC)c1
Agent: [Pd]
Agent: O=[PH2]O
Solvent: CC(C)(C)N
Solvent: CO
Product: CCC(C)(C)c1cc(-n2nc3ccccc3n2)c(O)c(C(C)(C)CC)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 99.8 %

Procedure:
To a 500 mL capacity stainless steel autoclave equipped with a stirrer, external heating jacket and internal heating and cooling coils are added 5.0 g (0.013 mole) of 2-nitro-2'-hydroxy-3',5'-di-tert-amylazobenzene, 0.25 g (dry weight) of (4% Pd/C+1% Pt/C) catalyst, 3.82 g (0.052 mole, 4 equivalent) of tert-butylamine, 5.16 g (0.039 mole, 3 equivalent) of aqueous hypophosphorous acid and 150 mL of methanol. The autoclave is purged with nitrogen gas and then hydrogen gas and then sealed and charged with hydrogen gas to a pressure of 53,000 Kg/m2. The reaction is stirred at room temperature and at 53,000 Kg/m2 pressure (recharging if necessary) for one hour. After one hour the temperature is raised to 50° C. and held at the same temperature and pressure for an additional 12 hours. Then the autoclave and its contents are cooled to 45°-47° C., removed and filtered through a Celite filter-aid pad to remove the catalyst. The catalyst and the residue on the filter pad are further washed with some ethyl acetate for complete recovery of the product. The organic solvents are removed on a rotary evaporator. The residue is diluted with about 500 mL of brine (saturated aqueous sodium chloride solution) and treated with hydrochloric acid dropwise until the Congo Red Indicator paper turns blue. The light brown insoluble material (the desired product) was filtered on a sintered glass funnel, washed with cold distilled water to remove any contaminated salt, and air-dried. This crude solid material was recrystallized from isopropanol/water to obtain 4.56 g of 2-(2'-hydroxy-3',5'-di-tert-amylphenyl)benzotriazole as white solid (yield 99%; melting point 80°-81° C.) showing a retention time of 25.89 min. in HPLC analysis.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:33]=[CH:32][C:6]([CH2:7][O:8][C:9]([C:11]2[N:16]3[C:17](=[O:29])[C@@H:18]([NH:19]C(=O)CC4C=CC=CC=4)[C@H:15]3[S:14][CH2:13][C:12]=2[CH2:30][Cl:31])=[O:10])=[CH:5][CH:4]=1.CN1CCOCC1.[C:41]([O:45][C:46]([NH:48][C:49]1[S:50][CH:51]=[C:52]([C:54](=[N:58][O:59][C:60]([C:63]([O:65][CH:66]([C:73]2[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=2)[C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=2)=[O:64])([CH3:62])[CH3:61])[C:55](O)=[O:56])[N:53]=1)=[O:47])([CH3:44])([CH3:43])[CH3:42].C1C=CC(OP(Cl)(Cl)=O)=CC=1>ClCCl.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][O:8][C:9]([C:11]2[N:16]3[C:17](=[O:29])[C@@H:18]([NH:19][C:55](=[O:56])[C:54]([C:52]4[N:53]=[C:49]([NH:48][C:46]([O:45][C:41]([CH3:42])([CH3:43])[CH3:44])=[O:47])[S:50][CH:51]=4)=[N:58][O:59][C:60]([C:63]([O:65][CH:66]([C:73]4[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=4)[C:67]4[CH:68]=[CH:69][CH:70]=[CH:71][CH:72]=4)=[O:64])([CH3:61])[CH3:62])[C@H:15]3[S:14][CH2:13][C:12]=2[CH2:30][Cl:31])=[O:10])=[CH:32][CH:33]=1
Reactant: COc1ccc(COC(=O)C2=C(CCl)CS[C@@H]3[C@H](NC(=O)Cc4ccccc4)C(=O)N23)cc1
Reactant: CC(C)(C)OC(=O)Nc1nc(C(=NOC(C)(C)C(=O)OC(c2ccccc2)c2ccccc2)C(=O)O)cs1
Agent: O=P(Cl)(Cl)Oc1ccccc1
Solvent: ClCCl
Solvent: O
Solvent: CN1CCOCC1
Product: COc1ccc(COC(=O)C2=C(CCl)CS[C@@H]3[C@H](NC(=O)C(=NOC(C)(C)C(=O)OC(c4ccccc4)c4ccccc4)c4csc(NC(=O)OC(C)(C)C)n4)C(=O)N23)cc1
Yield: 108.4 %

Procedure:
To a suspension of 7β-amino-3-chloromethyl-3-cephem-4-carboxylic acid p-methoxybenzyl ester (1) hydrochloride (72.1 g; 171 mMol.) in dichloromethane (1200 ml) are added N-methylmorpholin (18.8 ml; 1 Eq.) and 2-(2-t-butoxycarbonylamino-4-thiazolyl)-2-(1-diphenylmethoxycarbonyl-1-methylethoxyimino)acetic acid (95.5 g; 1.3 Eq.) at 0° C. and then phenylphosphoric acid dichloride (33.2 ml; 1.3 Eq.) and N-methylmorpholin (56.4 ml; 3 Eq.) at -40° C., and the mixture is stirred at -40° to -25° C. for 50 minutes. The reaction mixture is diluted with water. The formed dichloromethane layer is taken, washed with hydrochloric acid, water, aqueous sodium hydrogen carbonate, and water, dried, and concentrated under reduced pressure to give 7β-[2-(2-t-butoxycarbonylaminothiazol-4-yl)-2-(1-diphenylmethoxycarbonyl-1-methylethoxyimino)acetamido]-3-chloromethyl-3-cephem-4-carboxylic acid p-methoxybenzyl ester (2) (165 g).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[CH3:12])[C:5]([O:7][CH3:8])=[O:6].B([C:16]1[CH:24]=[CH:23][C:19]([C:20]([OH:22])=[O:21])=[CH:18][CH:17]=1)(O)O.C(N(CC)CC)C>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:8][O:7][C:5]([C:4]1[CH:9]=[CH:10][C:11]([CH3:12])=[C:2]([C:16]2[CH:24]=[CH:23][C:19]([C:20]([OH:22])=[O:21])=[CH:18][CH:17]=2)[CH:3]=1)=[O:6]
Reactant: O=C(O)c1ccc(B(O)O)cc1
Reactant: COC(=O)c1ccc(C)c(Br)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(C)c(-c2ccc(C(=O)O)cc2)c1
Temperature: 100 °C
Yield: 71.3 %

Procedure:
A stirred solution of methyl 3-bromo-4-methylbenzoate (2.6 g, 0.011 mole) in dry DMF (20 ml) under argon was treated with 4-boronobenzoic acid (1.85 g, 0.011 mole) and tetrakis (triphenylphosphine) palladium (O) (400 mg), followed by triethylamine (4.68 ml, 0.046 mole). The mixture was heated at 100° C. for 18 hours, then concentrated in vacuo. The residue was treated with ethyl acetate and extracted with 10% NaHCO3 solution. The basic extract was acidified with dil. HCl and extracted with ethyl acetate. The extract was dried (Na2SO4) and concentrated in vacuo to afford the title compound as a light orange solid (2.12 g, 85%).
Reaction SMILES: CC1(C)CC(C[N:10]=C=O)(C)CC(N=C=O)C1.[C:17]([O:21][CH2:22][CH2:23]O)(=[O:20])[CH:18]=[CH2:19]>>[C:17]([OH:21])(=[O:20])[CH:18]=[CH2:19].[NH2:10][C:17]([O:21][CH2:22][CH3:23])=[O:20]
Reactant: CC1(C)CC(N=C=O)CC(C)(CN=C=O)C1
Reactant: C=CC(=O)OCCO
Product: C=CC(=O)O
Product: CCOC(N)=O

Procedure:
A urethane acrylate was prepared with IPDI, hydroxyethyl acrylate and a 1000 MW polyether diol in an equivalent ratio of 6/5/1. The reaction product was a clear, colorless liquid. At 25° C. the viscosity was 166,000 cps.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([C:16]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)=O)=[CH:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])=[CH:5][CH:4]=1.Cl.[NH2:27][OH:28].C(=O)(O)[O-].[Na+]>CO.O>[OH:28][N:27]=[C:16]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)[C:9]([C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)=[CH:10][CH2:11][C:12]([O:14][CH3:15])=[O:13]
Reactant: COC(=O)CC=C(C(=O)c1ccc(OC)cc1)c1ccc(OC)cc1
Reactant: NO
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COC(=O)CC=C(C(=NO)c1ccc(OC)cc1)c1ccc(OC)cc1
Yield: 89.9 %

Procedure:
A mixture of 24.5 g of methyl 4,5-bis(4-methoxyphenyl)-5-oxo-3-pentenoate and 51.5 g of hydroxylamine hydrochloride in a mixture of 650 ml of methanol and 72 ml of water was heated under reflux for 23 hours. During this procedure, 0.9 equivalent of sodium bicarbonate was added portionwise to the reaction mixture as the reaction progressed. After completion of the reaction, methanol was evaporated under reduced pressure. Water and ethyl acetate were added to the residue for dissolution thereof, the organic layer was separated, washed with saturated brine and dried over anhydrous magnesium sulfate. The organic layer was then concentrated under reduced pressure and the residue was separated and purified by silica gel column chromatography (ethyl acetate:hexane=1:1) to give 23 g (yield 90%) of methyl 5-hydroxyimino-4,5-bis(4-methoxyphenyl)-3-pentenoate as an oil.
Reaction SMILES: [CH3:1][CH2:2][C:3]1[C:21]2=[N:22][C:5](=[CH:6][C:7]3[NH:11][C:10]([CH:12]=[C:13]4[CH:34]([CH3:35])[CH:33]([CH2:36][CH2:37][C:38]([O:40][CH3:41])=[O:39])[C:15]([C:16]5[CH:27](C(OC)=O)[C:25](=[O:26])[C:24]6[C:17]=5[NH:18][C:19]([C:23]=6[CH3:32])=[CH:20]2)=[N:14]4)=[C:9]([CH3:42])[C:8]=3[CH:43]=[CH2:44])[C:4]=1[CH3:45]>N1C=CC=CC=1>[CH3:1][CH2:2][C:3]1[C:21]2=[N:22][C:5](=[CH:6][C:7]3[NH:11][C:10]([CH:12]=[C:13]4[C@@H:34]([CH3:35])[C@H:33]([CH2:36][CH2:37][C:38]([O:40][CH3:41])=[O:39])[C:15]([C:16]5[CH2:27][C:25](=[O:26])[C:24]6[C:17]=5[NH:18][C:19]([C:23]=6[CH3:32])=[CH:20]2)=[N:14]4)=[C:9]([CH3:42])[C:8]=3[CH:43]=[CH2:44])[C:4]=1[CH3:45]
Reactant: C=Cc1c(C)c2cc3nc(c4c5[nH]c(cc6nc(cc1[nH]2)C(C)=C6CC)c(C)c5C(=O)C4C(=O)OC)C(CCC(=O)OC)C3C
Solvent: c1ccncc1
Product: C=Cc1c(C)c2cc3nc(c4c5[nH]c(cc6nc(cc1[nH]2)C(C)=C6CC)c(C)c5C(=O)C4)[C@@H](CCC(=O)OC)[C@@H]3C
Temperature: 25 °C
Yield: 99.4 %

Procedure:
To a solution of methyl pheophorbide-a (2.0 g, 3.3 mmol) in pyridine (80 mL) was added distilled water (0.8 mL) and the mixture was refluxed under argon with stirring. The reaction was monitored by HPLC (Waters instrument, hexane-acetone, 90:10-mobile phase; LiChrospher CN-column; detection at 410 nm). The HPLC of reaction aliquot after 8.5 h of reflux showed <1% (peak area) of starting methyl pheophorbide-a. The reaction was stopped, cooled to room temperature and solvent removed under reduced pressure. The residue was precipitated from methylene chloride-hexane to give methyl pyropheophorbide-a (1.8 g, 100%).
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:8](O)([CH3:10])[CH3:9].B(F)(F)F>P(=O)(O)(O)O>[CH:8]([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=1[OH:7])([CH3:10])[CH3:9]
Reactant: CC(C)O
Reactant: Oc1ccccc1
Agent: FB(F)F
Agent: O=P(O)(O)O
Product: CC(C)c1ccccc1O

Procedure:
A process according to claim 1 wherein phenol is reacted with isopropanol in the presence of a diethyl ether complex of boron trifluoride in phosphoric acid diluent at a temperature of between about 70°-90° C. to produce ortho-isopropyl phenol.
Reaction SMILES: C([O:4][CH:5]([CH:12]=[CH2:13])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)(=O)C.[OH-].[Na+].C(O)C>COC1C=CC(O)=CC=1.O>[CH:12]([CH:5]([OH:4])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[CH2:13]
Reactant: C=CC(OC(C)=O)c1ccccc1
Agent: COc1ccc(O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: C=CC(O)c1ccccc1
Temperature: 65 °C
Yield: 90 %

Procedure:
120 grams (0.6876 mol) of vinylbenzyl acetate, inhibited with 10 mg of MEHQ were added to a one liter 3-neck round bottom flask equipped with a condenser, mechanical stirrer and thermometer, followed by 50 grams (1.25 mol) of sodium hydroxide. 50 mL of water and 300 mL of ethanol were then added and the contents of the flask heated at reflux (65° C.) for 2 hours. After the mixture was allowed to cool to room temperature, water was added. The content of the flask was poured into a separatory funnel and extracted with chloroform several times. The chloroform extract was subsequently washed several times with water and dried over magnesium sulfate. Removal of the chloroform on the rotary evaporator afforded 83 grams of the vinylbenzyl alcohol product (95% yield). The purification was accomplished by vacuum distillation.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[CH:4][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[N:6][CH:7]=1.C1C(=O)N([Br:23])C(=O)C1.CC(N=NC(C#N)(C)C)(C#N)C>C(Cl)(Cl)(Cl)Cl>[Br:23][CH2:1][C:2]1[N:3]=[CH:4][C:5]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[N:6][CH:7]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1cnc(NC(=O)OC(C)(C)C)cn1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)(C)OC(=O)Nc1cnc(CBr)cn1
Temperature: 80 °C
Reaction time: 4 h
Yield: 75.5 %

Procedure:
To a solution tert-butyl 5-methylpyrazin-2-ylcarbamate (500 mg, 2.39 mmol) in CCl4 (8.0 mL) were added NBS(446 mg, 2.51 mmol) and AIBN (117 mg, 0.72 mmol). The reaction mixture was stirred for 4 hours at 80° C. after which, it was partitioned between CH2Cl2 and water. The organic layer was separated and the aqueous layer was extracted with CH2Cl2. The combined organic extracts were washed with brine, dried over MgSO4, celite filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography using (10% Ethyl acetate/Hexane) as a solvent to afford title compound (520 mg, 75% yield). 1H NMR (600 MHz, CDCl3) δ 9.29 (s, 1H), 8.95 (s, 1H), 8.37 (s, 1H), 4.38 (s, 2H), 1.57 (s, 9H). MS m/z: 288 [M+1].