Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:14]([OH:16])=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]C(O)=O.O[N:18]1C2C=CC=CC=2N=N1.Cl.C(N(CC)CC)C.C[N:36](C)[CH:37]=[O:38]>ClCCl>[CH2:1]([C:14]([NH2:18])=[O:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:37]([NH2:36])=[O:38]
Reactant: CN(C)C=O
Reactant: On1nnc2ccccc21
Reactant: O=C(O)CCCCCCCCCCC(=O)O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: NC(=O)CCCCCCCCCCC(N)=O
Reaction time: 1 h

Procedure:
0.46 g (2 mmol) of 1,10-decanedicarboxylic acid and 0.674 g (4.4 mol) of 1-hydroxybenzotriazole were dissolved in N,N-dimethylformamide, and 10 ml of a dichloromethane solution containing 0.90 g (4.4 mmol) of 1-ethyl-3-(3-dimethylaminopropyl) carboimido hydrochloride was added at −5 degree C. with stirring. After 1 hour, 10 ml of dichloromethane solution containing 1.51 g (4.4 mmol) of the above L-valyl-L-valinebenzylester hydrochloride followed by 0.62 ml (4.4 mmol) of triethylamine were added, and stirred for 24 hours while gradually returning to room temperature. The solvent was completely distilled off under reduced pressure, and the white precipitate obtained was washed on filter paper successively with 50 ml of 10 wt % citric acid aqueous solution, 20 ml water, 50 ml of 4 wt % sodium bicarbonate aqueous solution and 20 ml water. 0.98 g of N,N′-bis (L-valyl-L-valinebenzylester) decane-1,10-dicarboxamide was obtained as a white solid (yield 0.61%). 0.5 g (0.62 mmol) of this compound was dissolved in 100 ml dimethylformamide, 0.25 g of 10 wt % palladium/carbon was added as a catalyst, and catalytic hydrogenation was performed. After 6 hours, the catalyst was filtered off using cerite, and the solvent was distilled off under reduced pressure to obtain a colorless oil. The oil obtained was crystallized using a water-ethanol mixed solvent to give a white solid. After analysis, this white solid was N,N′-bis (L-valyl-L-valine) decane-1,10-dicarboxamide (corresponds to m=2, n=10 in general formula (1)).
Reaction SMILES: [OH:1][C:2]1[CH:12]=[CH:11][C:5]2[C:6](=[O:10])[CH2:7][CH2:8][O:9][C:4]=2[C:3]=1[CH2:13][CH2:14][CH3:15].C([O:18][C:19](=[O:45])[CH2:20][CH2:21][CH2:22][C:23](=[O:44])[C:24]1[CH:29]=[CH:28][C:27]([O:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]Br)=[C:26]([CH2:37][CH2:38][C:39]([O:41]CC)=[O:40])[CH:25]=1)C>CCCCCC.C(OCC)(=O)C>[C:39]([CH2:38][CH2:37][C:26]1[CH:25]=[C:24]([C:23](=[O:44])[CH2:22][CH2:21][CH2:20][C:19]([OH:45])=[O:18])[CH:29]=[CH:28][C:27]=1[O:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][O:1][C:2]1[CH:12]=[CH:11][C:5]2[C:6](=[O:10])[CH2:7][CH2:8][O:9][C:4]=2[C:3]=1[CH2:13][CH2:14][CH3:15])([OH:41])=[O:40]
Reactant: CCCc1c(O)ccc2c1OCCC2=O
Reactant: CCOC(=O)CCCC(=O)c1ccc(OCCCCCBr)c(CCC(=O)OCC)c1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: CCCc1c(OCCCCCOc2ccc(C(=O)CCCC(=O)O)cc2CCC(=O)O)ccc2c1OCCC2=O
Yield: 53.5 %

Procedure:
Starting with 0.135 g (0.66 mmol) of 2,3-dihydro-7-hydroxy-8-propyl-4H-1-benzopyran-4-one, and 0.31 g (0.64 mmol) of 4-[(5-bromopentyl)oxy]-3-(3-ethoxy-3-oxopropyl)-δ-oxobenzenepentanoic acid ethyl ester, the title compound (0.190 g; 62.8% overall yield) was obtained as a white solid, mp 151°-153.5° C. (recrystallized from hexane-ethyl acetate), using the procedure of example 22.
Reaction SMILES: [CH3:1][C:2]1([CH3:17])[O:16][CH:13]([CH:14]=[CH2:15])[CH:4]([CH:5]([O:9][CH2:10][O:11][CH3:12])[CH2:6][CH:7]=O)[O:3]1.Cl.[NH2:19][OH:20]>N1C=CC=CC=1.C(OCC)C>[CH3:1][C:2]1([CH3:17])[O:16][CH:13]([CH:14]=[CH2:15])[CH:4]([CH:5]([O:9][CH2:10][O:11][CH3:12])[CH2:6][CH:7]=[N:19][OH:20])[O:3]1
Reactant: NO
Reactant: C=CC1OC(C)(C)OC1C(CC=O)OCOC
Agent: Cl
Solvent: c1ccncc1
Solvent: CCOCC
Product: C=CC1OC(C)(C)OC1C(CC=NO)OCOC
Reaction time: 8 h
Yield: 91.7 %

Procedure:
The above 4,5-(dimethylmethylenedioxy)-3-methoxymethoxy-6-heptenal (91.9 mg) was dissolved in 1 ml of pyridine, and 45 mg of hydroxylamine hydrochloride was added at room temperature, and stirring was conducted at room temperature for 8 hours. The reaction mixture was diluted with diethyl ether. The diluted reaction mixture was washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to afford 89.5 mg of 4,5-(dimethylmethylenedioxy)-3-methoxymethoxy-6-heptenal oxime having the following properties (yield 52%).
Reaction SMILES: [BH4-].[Na+].[CH2:3]([O:10][C:11]1[C:18]([O:19][CH3:20])=[CH:17][CH:16]=[CH:15][C:12]=1[CH:13]=[O:14])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.O.Cl>C(O)C.C(OCC)C>[CH2:3]([O:10][C:11]1[C:12]([CH2:13][OH:14])=[CH:15][CH:16]=[CH:17][C:18]=1[O:19][CH3:20])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: COc1cccc(C=O)c1OCc1ccccc1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Solvent: CCOCC
Product: COc1cccc(CO)c1OCc1ccccc1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 100.1 %

Procedure:
To a well-stirred suspension of 2.0 g (52.7 mmol) of sodium borohydride in 65 mL of ethyl alcohol at 0° C. under a nitrogen atmosphere, was slowly added 15 g (61.9 mmol) of 2-benzyloxy-3-methoxybenzaldehyde, from Step 1, in 100 mL of ethyl alcohol. The reaction mixture was stirred at 0° C. for 10 minutes and then 50 mL of water was added to quench the reaction, followed by 50 mL of diethyl ether. The mixture was slowly added to 60 mL of 10% aqueous hydrochloric acid solution at 0° C. and the resultant mixture was stirred for 1 h and then extracted with 3×200 mL of diethyl ether. The combined ether extracts were washed with aqueous sodium bicarbonate solution, water and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give 15.14 g (100% yield) of the title compound as a white solid.
Reaction SMILES: [CH2:1]([CH:3]([C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[CH:8][N:7]=1)[CH2:4][CH3:5])[CH3:2].O[CH2:17][NH:18][C:19](=[O:23])[CH:20]([Cl:22])[Cl:21]>>[CH2:1]([CH:3]([C:6]1[C:15]2[C:10](=[C:11]([CH2:17][NH:18][C:19](=[O:23])[CH:20]([Cl:22])[Cl:21])[CH:12]=[CH:13][CH:14]=2)[CH:9]=[CH:8][N:7]=1)[CH2:4][CH3:5])[CH3:2]
Reactant: O=C(NCO)C(Cl)Cl
Reactant: CCC(CC)c1nccc2ccccc12
Product: CCC(CC)c1nccc2c(CNC(=O)C(Cl)Cl)cccc12

Procedure:
1-(1-Ethylpropyl)isoquinoline and N-hydroxymethyl dichloroacetamide were reacted in the same way as in step (b) of Example 18 to afford 1-(1-ethylpropyl)-5-dichloroacetylaminomethylisoquinoline. The product was successively reacted in the same way as in steps (c), (d), (e) and (f) of Example 18 to afford 1-(1-ethylpropyl)-isoquinoline-5-acetonitrile. The product was treated in the same way as in Example 3 to afford 1-(1-ethylpropyl)-isoquinoline-5-acetic acid as an oil. The hydrochloride of the product was in the form of colorless prisms having a melting point of 107° to 109° C.
Reaction SMILES: [CH:1]1[C:6]2[C:7]3[C:15](=[O:16])[O:14][C:12](=[O:13])[C:8]=3[CH2:9][CH2:10][CH2:11][C:5]=2[CH:4]=[CH:3][CH:2]=1.[CH3:17][C:18]([CH3:23])([CH2:21][NH2:22])[CH2:19][OH:20].O>C1(C)C=CC=CC=1>[OH:20][CH2:19][C:18]([CH3:23])([CH3:17])[CH2:21][N:22]=[C:12]([C:8]1[CH2:9][CH2:10][CH2:11][C:5]2[CH:4]=[CH:3][CH:2]=[CH:1][C:6]=2[C:7]=1[C:15]([OH:14])=[O:16])[OH:13]
Reactant: O=C1OC(=O)C2=C1CCCc1ccccc12
Reactant: CC(C)(CN)CO
Solvent: O
Solvent: Cc1ccccc1
Product: CC(C)(CO)CN=C(O)C1=C(C(=O)O)c2ccccc2CCC1
Temperature: 25 °C

Procedure:
21.4 g (0.1 mol) of 6,7-dihydro-5H-benzocycloheptene-8,9-dicarboxylic acid anhydride and 10.3 g (0.1 mol) of 2,2-dimethyl-3-aminopropanol are dissolved in 60 ml of toluene and the solution is refluxed for 1 hour, the water formed being separated off by means of a water separator downstream of the reaction vessel. After cooling to room temperature, the crystals which have precipitated out are filtered off. This yields 28.9 g (96.6% of theory) of N-(3'-hydroxy-2',2'-dimethylpropyl)-6,7-dihydro-5H-benzocycloheptene-8,9-dicarboxylic acid imide.
Reaction SMILES: [CH3:1][N:2]([CH3:12])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[O:11])[C:8]([CH3:10])=[CH2:9].[CH2:13]1[S:18](=[O:20])(=[O:19])[O:17][CH2:16][CH2:15][CH2:14]1.CC(C)=O.CO>C(#N)C>[S:18]([CH2:13][CH2:14][CH2:15][CH2:16][N+:2]([CH2:3][CH2:4][CH2:5][NH:6][C:7](=[O:11])[C:8]([CH3:10])=[CH2:9])([CH3:12])[CH3:1])([O-:17])(=[O:20])=[O:19]
Reactant: C=C(C)C(=O)NCCCN(C)C
Reactant: O=S1(=O)CCCCO1
Solvent: CC(C)=O
Solvent: CC#N
Solvent: CO
Product: C=C(C)C(=O)NCCC[N+](C)(C)CCCCS(=O)(=O)[O-]
Temperature: 70 °C
Reaction time: 1 h
Yield: 85.5 %

Procedure:
In 380 ml of acetonitrile were dissolved 130 g (0.764 mol) of N-[3-(dimethylamino)propyl]methacrylamide, 104 g of butanesultone and 234 mg of 4-hydroxy-2,2,6,6-tetramethylpiperidinoxy and the solution was heated at 70° C. for 6 hours. After allowing to cooling, to the reaction mixture were added 1,350 ml of acetone and 150 ml of methanol and the mixture was stirred at room temperature for one hour. The crystals deposited were collected by filtration and thoroughly washed with acetone to obtain 200.0 g (yield: 85%) of 4-sulfonatobutyl[3-(methacryloylamino)propyl]dimethylammonium.
Reaction SMILES: [Al:1].[OH:2][S:3]([C:6]([F:9])([F:8])[F:7])(=[O:5])=[O:4]>O>[O-:5][S:3]([C:6]([F:9])([F:8])[F:7])(=[O:4])=[O:2].[Al+3:1].[O-:5][S:3]([C:6]([F:9])([F:8])[F:7])(=[O:4])=[O:2].[O-:5][S:3]([C:6]([F:9])([F:8])[F:7])(=[O:4])=[O:2]
Reactant: [Al]
Reactant: O=S(=O)(O)C(F)(F)F
Solvent: O
Product: O=S(=O)([O-])C(F)(F)F
Product: [Al+3]
Reaction time: 48 h

Procedure:
0.2 g of aluminium powder and 70 ml of water are introduced with stirring into a 250-ml glass flask. The suspension obtained is brought to 80° C., then 33.3 ml of an aqueous solution of 0.57N triflic acid is added drop by drop. This mixture is maintained with stirring at 80° C. for 2 hours, then at ambient temperature for 48 hours. The aluminium triflate obtained may then be isolated by eliminating the excess aluminium by filtration and evaporating the water at 100° C. under atmospheric pressure. In this way one recovers 3.5 g of aluminium triflate, having the formula Al(CF3SO3)3, in the form of a white powder.
Reaction SMILES: [O-]S([O-])(=O)=O.[Na+].[Na+].[CH3:8][C:9]([CH3:13])([CH3:12])[CH:10]=O.[NH2:14][CH:15]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C(Cl)Cl>[CH3:8][C:9]([CH3:13])([CH3:12])[CH:10]=[N:14][CH:15]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: CC(C)(C)C=O
Reactant: NC(c1ccccc1)c1ccccc1
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)(C)C=NC(c1ccccc1)c1ccccc1

Procedure:
A 100-mL round-bottomed flask containing a stir bar was charged with Na2SO4 (8.0 g) and CH2Cl2 (40 mL). Trimethylacetaldehyde (8) (7.65 mL, 52 mmol, 1.3 equiv) and aminodiphenylmethane (9) (6.89 mL, 40 mmol, 1.0 equiv) were added sequentially via syringe while stirring. The flask was capped with a plastic stopper, and the mixture was stirred at room temperature. The mixture became cloudy after 5 min. After stirring for 1 h, the solution was decanted into a 200-mL round-bottomed flask, rinsing with CH2Cl2 (4×5 mL) and concentrated to 8-10 mL using a rotary evaporator. The flask was then maintained at 1 torr for 10 min. A 5-cm diameter fritted disk funnel was filled with a 2-cm high layer of silica gel. The funnel was rinsed with a solution of 20:1:0.5 hexanes/Et2O/triethylamine (50 mL) under reduced pressure, followed by a solution of 20:1 hexanes/Et2O (50 mL). The oil prepared above was dissolved in 20:1 hexanes/Et2O (25 mL) and rinsed through the frit into a tared 250-mL round-bottomed flask under reduced pressure, rinsing with 20:1 hexanes/Et2O (4×25 mL). The mixture was concentrated (30 torr→1 torr) to provide a clear, pale yellow oil that solidified into a white solid. The solid was broken up into approximately 1-cm diameter pieces using a spatula, and was maintained at 1 torr for another 15 min to provide N-(2,2-dimethyl propylidene)diphenylmethanamine (2a) as a white solid in approximately 98% 1H-NMR purity. The product was used in the next step without further purification. Yield: 9.93 g (39.6 mmol, 99%).
Reaction SMILES: [OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]([CH2:20][CH2:21][CH2:22][O:23][C:24]3[CH:29]=[CH:28][C:27]([O:30][CH2:31][CH2:32][S:33][CH2:34][CH2:35][CH2:36][C:37]([F:43])([F:42])[C:38]([F:41])([F:40])[F:39])=[CH:26][CH:25]=3)[C:7]([C:13]3[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=3)([CH3:12])[CH2:8][S:9]2)=[CH:4][CH:3]=1.[OH:44]OS([O-])=O.[K+].O>O1CCCC1.O>[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]([CH2:20][CH2:21][CH2:22][O:23][C:24]3[CH:29]=[CH:28][C:27]([O:30][CH2:31][CH2:32][S:33]([CH2:34][CH2:35][CH2:36][C:37]([F:43])([F:42])[C:38]([F:39])([F:40])[F:41])=[O:44])=[CH:26][CH:25]=3)[C:7]([C:13]3[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=3)([CH3:12])[CH2:8][S:9]2)=[CH:4][CH:3]=1
Reactant: CC1(c2ccc(O)cc2)CSc2cc(O)ccc2C1CCCOc1ccc(OCCSCCCC(F)(F)C(F)(F)F)cc1
Reactant: O=S([O-])OO
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: CC1(c2ccc(O)cc2)CSc2cc(O)ccc2C1CCCOc1ccc(OCCS(=O)CCCC(F)(F)C(F)(F)F)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 57 %

Procedure:
(3RS,4RS)-7-Hydroxy-3-(4-hydroxyphenyl)-3-methyl-4-{3-{4-[2-(4,4,5,5,5-pentafluoropentylthio)ethoxy]phenoxy}propyl}thiochroman (11) prepared in Step 8 (110 mg, 0.17 mmol) was dissolved in tetrahydrofuran (5 ml), which was then cooled down to 0° C. Oxone® (monopersulfate compound; DuPont product) (63 mg, 0.1 mmol) and water (3 drops) were added thereto, and the resulting mixture was stirred for 1 hour. Water (2 drops was further added, and the mixture was stirred for 1 hour. Water was added to the reaction solution and the resulting mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, concentrated, and subjected to silica gel column chromatography to give (3RS,4RS)-7-hydroxy-3-(4-hydroxyphenyl)-3-methyl-4-{3-{4-[2-(4,4,5,5,5-pentafluoropentylsulfinyl)ethoxy]phenoxy}propyl}thiochroman (12) (64.5 mg, yield 57%) as a colorless foamy substance.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:26]([F:29])([F:28])[F:27])[O:13][N:12]=[C:11]([C:14]3[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[C:16]([CH2:23][O:24][CH3:25])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.C(Cl)(=O)C(Cl)=O.C[N:37](C)C=O>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([C:26]([F:29])([F:28])[F:27])[O:13][N:12]=[C:11]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([NH2:37])=[O:19])=[C:16]([CH2:23][O:24][CH3:25])[CH:15]=3)[CH2:10]2)[CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: CN(C)C=O
Reactant: COCc1cc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)ccc1C(=O)O
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Product: COCc1cc(C2=NOC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)ccc1C(N)=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 92.6 %

Procedure:
In a solution of 0.80 g of 4-[5-(3,5-dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-methoxymethyl benzoic acid in 30 mL of dichloromethane, 0.23 g of oxalyl chloride and 0.06 g of N,N-dimethylforamide were added, and stirred at room temperature for 30 minutes. After the completion of the reaction, the solvent was distilled off under reduced pressure, the residue was dissolved in 5 mL of tetrahydrofuran, and a solution of 1.50 g of concentrated ammonia water in 10 mL of tetrahydrofuran was added dropwise at room temperature with stirring. After the completion of the addition dropwise, it was continued to stir further for 1 hour. After the completion of the reaction, the solvent was distilled off under reduced pressure, 10 mL of water was added in the residue, and extracted with ethyl acetate (20 mL×1). The organic phase was washed with 10 mL of 2N hydrochloric acid, and then dehydrated with and dried over saturated sodium chloride aqueous solution and then anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified with silica gel column chromatography that were eluated with ethyl acetate-hexane (1:1) to obtain 0.34 g of the aimed product as white crystal.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][CH:3]=1.C([Li])CCC.[CH3:14][C:15]([S:18]([N:20]=[C:21]1[CH2:24][O:23][CH2:22]1)=[O:19])([CH3:17])[CH3:16].[Cl-].[NH4+]>O1CCCC1.ClCCl.O>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([C:21]2([NH:20][S:18]([C:15]([CH3:17])([CH3:16])[CH3:14])=[O:19])[CH2:24][O:23][CH2:22]2)=[CH:3][CH:4]=1
Reactant: CC(C)(C)S(=O)N=C1COC1
Reactant: Brc1ccc(Br)cc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: O
Solvent: C1CCOC1
Solvent: ClCCl
Product: CC(C)(C)S(=O)NC1(c2ccc(Br)cc2)COC1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
To a 50 mL round-bottomed flask was added 1,4-dibromobenzene (2.85 g, 12.07 mmol) in tetrahydrofuran (40.2 ml). The solution was cooled to −78° C. and n-butyl lithium (4.51 ml, 11.26 mmol) was added dropwise. The mixture was stirred for 1 hour at −78° C. 2-methyl-N-(oxetan-3-ylidene)propane-2-sulfinamide (1.41 g, 8.05 mmol) was added as a tetrahydrofuran solution (ca 1 ml) and the reaction was stirred for 10 minutes and warmed to room temperature. Saturated ammonium chloride was added followed by water and dichloromethane. The aqueous layer was extracted twice with dichloromethane and the combined organics were dried with magnesium sulfate, filtered and concentrated under vacuum. The residue was purified by regular phase, flash column chromatography to give the title compound.
Reaction SMILES: [C:1]1(=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[CH:3]=[CH:2]1.S(=O)(=O)(O)O.[N+:18]([O-])([OH:20])=[O:19]>O>[N+:18]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:5]=1[C:4](=[O:11])[CH:3]=[CH:2][C:1]2=[O:12])([O-:20])=[O:19]
Reactant: O=[N+]([O-])O
Reactant: O=C1C=CC(=O)c2ccccc21
Agent: O=S(=O)(O)O
Solvent: O
Product: O=C1C=CC(=O)c2c1cccc2[N+](=O)[O-]

Procedure:
The same procedure as in Example 1 was repeated except that 10.0 g of 1,4-naphthoquinone was added to 200 g of a mixed acid consisting of 83 percent by weight of sulfuric acid, 4 percent by weight of nitric acid and 13 percent by weight of water with maintaining a temperature of 5° to 10°C, to obtain 8.9 g of brown-colored crude 5-nitro-1,4-naphthoquinone of a melting point of 140°C. The D.V.S. of the reaction mixture after reaction was 6.1. The crude product was purified to obtain the similar results with Example 1.
Reaction SMILES: [OH-:1].[Na+].[CH2:3]1[CH:7]2[C@H:8]3[C:13](=[O:14])[O:12][C:10](=[O:11])[C@H:9]3[CH:4]1[CH:5]=[CH:6]2.O1CCCC1.[Br:20]Br>O>[Br:20][CH:6]1[CH:5]2[CH:4]3[CH:9]([CH:8]([C:13]([OH:12])=[O:14])[CH:7]1[CH2:3]3)[C:10](=[O:11])[O:1]2
Reactant: [OH-]
Reactant: BrBr
Reactant: O=C1OC(=O)[C@H]2C3C=CC(C3)[C@@H]12
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)C1C2CC3C(OC(=O)C31)C2Br
Temperature: 45 °C
Reaction time: 0.08 h

Procedure:
In a 50-mL one neck round bottom flask, sodium hydroxide, Catalog No. 655104 from Aldrich Co. (0.33 g) was dissolved in water (37 mL). In the same flask, cis-endo-5-norbornene-2,3-dicarboxylic anhydride, Catalog No. 247634 from Aldrich Co. (2.54 g), and tetrahydrofuran (5 mL) were added. The flask was heated while stirring in a 45° C. water bath for five minutes to dissolve then cooled in an ice bath to 5° C. Bromine, Catalog No. 207888 from Aldrich Co. (2.55 g) was added dropwise to the flask. After stirring for 14 hours at room temperature, extract the product in ethyl acetate (100 mL) and dry with magnesium sulfate. The product, 2-bromo-5-oxo-4-oxatricyclo[4.2.1.03,7]nonane-9-carboxylic acid (3.86 g) was isolated by removing ethyl acetate by rotary evaporation.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH:11]=[CH:12][NH:13][C:14](=[O:15])[C:5]=3[C:4]=2[CH:3]=1.Cl[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1.[H-].[Na+]>CN(C=O)C>[F:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)[C:6]3[CH:11]=[CH:12][NH:13][C:14](=[O:15])[C:5]=3[C:4]=2[CH:3]=1
Reactant: O=c1[nH]ccc2[nH]c3ccc(F)cc3c12
Reactant: COc1ccc(CCl)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(Cn2c3ccc(F)cc3c3c(=O)[nH]ccc32)cc1
Yield: 62.9 %

Procedure:
8-Fluoro-2,5-dihydro-1H-pyrido[4,3-b]indol-1-one (I-64a: 0.15 g, 0.00074 mol) was reacted with 1-(chloromethyl)-4-methoxybenzene (0.14 g, 0.00092 mol), NaH (0.058 g, 0.058 mol) and DMF (10 mL) to afford the crude product. Purification by column chromatography on silica gel (1.5% methanol in DCM) afforded 0.15 g of the product (65.21% yield).
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([Br:10])=[CH:6][CH:5]=1)=[O:3].[CH:11](OC)(OC)[O:12]C.[CH3:18]O>>[Br:10][C:7]1[CH:8]=[CH:9][C:4]([C:2]([O:12][CH3:11])([O:3][CH3:18])[CH3:1])=[CH:5][CH:6]=1
Reactant: CC(=O)c1ccc(Br)cc1
Reactant: COC(OC)OC
Reactant: CO
Product: COC(C)(OC)c1ccc(Br)cc1

Procedure:
A mixture of 2 g (0.01 mole) of 4-bromoacetophenone, 5.6 ml of trimethyl orthoformate, 5.6 ml of methanol and 0.67 g of Amberlite® IR 120 is heated at reflux for 3 hours. After cooling, the mixture is filtered through Celite® and the filtered solution is evaporated. 2.4 g of the title compound are obtained in the form of an oil.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][CH2:10][CH2:11][C:12]2[CH:22]=[CH:21][CH:20]=[CH:19][C:13]=2[O:14][CH2:15][CH:16]2[CH2:18][O:17]2)[CH:5]=[CH:6][CH:7]=1.[CH3:23][NH:24][CH3:25]>O1CCCC1>[CH3:23][N:24]([CH3:25])[CH2:18][CH:16]([OH:17])[CH2:15][O:14][C:13]1[CH:19]=[CH:20][CH:21]=[CH:22][C:12]=1[CH2:11][CH2:10][CH2:9][CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[CH:3]=1
Reactant: CNC
Reactant: Cc1cccc(CCCCc2ccccc2OCC2CO2)c1
Solvent: C1CCOC1
Product: Cc1cccc(CCCCc2ccccc2OCC(O)CN(C)C)c1
Yield: 59 %

Procedure:
Following a procedure similar to that described in Example 1(b), 1.83 g of 2-{2-[4-(3-methylphenyl)butyl]phenoxymethyl}oxirane [prepared as described in step (a) above] dissolved in 20 ml of tetrahydrofuran were treated with 4 ml of 50% by volume aqueous dimethylamine. The crude product thus obtained was purified as described in Example 1(b), to give 1.25 g (yield 59%) of the title compound as a colorless oil.
Reaction SMILES: C(NC1SC=C(C(=NOCCN2CCOCC2)C(O)=O)N=1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[IH:40].N1C=CC=CC=1.C1(N=C=NC2CCCCC2)CCCCC1.C(OC[C:67]1[CH2:68][S:69][C@@H:70]2[CH:90](N)[C:89](=[O:92])[N:71]2[C:72]=1[C:73]([O:75]C(C1C=CC=CC=1)C1C=CC=CC=1)=[O:74])(=O)C>CN(C)C=O>[IH:40].[S:69]1[C@@H:70]2[CH2:90][C:89](=[O:92])[N:71]2[C:72]([C:73]([OH:75])=[O:74])=[CH:67][CH2:68]1
Reactant: CC(=O)OCC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)C(N)[C@H]2SC1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: I
Agent: O=C(O)C(=NOCCN1CCOCC1)c1csc(NC(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: O=C(O)C1=CCS[C@@H]2CC(=O)N12
Reaction time: 0.17 h

Procedure:
A solution of 1 g of the product of Step A, 0.38 g of pyridine hydroiodide, 0.63 g of dicyclohexylcarbodiimide, 0.60 g of benzhydryl 3-acetoxymethyl-7-amino-ceph-3-eme-4-carboxylate and 5 ml of anhydrous dimethylformamide was stirred at room temperature for 30 minutes and was vacuum filtered to remove dicyclohexylurea. 100 ml of ether were added to the filtrate and the mixture was stirred for 10 minutes and was vacuum filtered. The product was rinsed with ether and was chromatographed over silica gel. Elution with a 7-1 ethyl acetate-ethanol mixture yielded 0.524 g of the syn isomer of benzhydryl 3-acetoxymethyl-7-[2-2tritylamino-4-thiazolyl)-2-(2-morpholinoethoxyimino)-acetamido]-ceph-3-eme-4-carboxylate hydroiodide melting at 167° C. (decomposition).