Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH2:5][CH2:4][CH2:3][C@@H:2]1[CH2:6][OH:7].[C:8]1([CH3:18])[CH:13]=[CH:12][C:11]([S:14](Cl)(=[O:16])=[O:15])=[CH:10][CH:9]=1>C(Cl)Cl.N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[CH3:18][C:8]1[CH:13]=[CH:12][C:11]([S:14]([O:7][CH2:6][C@H:2]2[CH2:3][CH2:4][CH2:5][O:1]2)(=[O:16])=[O:15])=[CH:10][CH:9]=1
Reactant: OC[C@H]1CCCO1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)OC[C@H]2CCCO2)cc1
Temperature: 0 °C
Reaction time: 16 h

Procedure:
To a solution of the (R)-(tetrahydrofuran-2-yl)methanol (Aldrich, 12 g, 0.12 mol) in 40 mL CH2Cl2 and 40 mL pyridine was added 4-dimethylaminopyridine (DMAP, 0.72 g, 5.9 mmol). This mixture was cooled to 0° C. and p-toluenesulfonyl chloride (23.5 g, 0.123 mol) was added portionwise over 20 minutes. The mixture stirred at ambient temperature for 16 hours, then quenched with excess 5% aqueous HCl. The layers were separated and the aqueous layer was extracted with CH2Cl2 (3×10 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. Purification by column chromatography (SiO2, 65% hexanes in EtOAc) provided the title compound. MS (DCI/NH3) m/z 257 (M+H)+; m/z 274 (M+NH4)+.
Reaction SMILES: [Mg].[Cl:2][C:3]1[CH:8]=[CH:7][C:6](I)=[C:5]([Cl:10])[CH:4]=1.I/[C:12](=[CH:18]\[C:19]([O:21][CH2:22][CH3:23])=[O:20])/[C:13]([O:15][CH2:16][CH3:17])=[O:14]>C(OCC)C.CN(C=O)C.Cl.[Cl-].[Zn+2].[Cl-].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(Br)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:16]([O:15][C:13](=[O:14])/[C:12](/[C:6]1[CH:7]=[CH:8][C:3]([Cl:2])=[CH:4][C:5]=1[Cl:10])=[CH:18]/[C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH3:17]
Reactant: Clc1ccc(I)c(Cl)c1
Reactant: CCOC(=O)/C=C(\I)C(=O)OCC
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cl
Solvent: CCOCC
Solvent: CCBr
Solvent: CN(C)C=O
Product: CCOC(=O)/C=C(/C(=O)OCC)c1ccc(Cl)cc1Cl
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 70.4 %

Procedure:
A suspension of magnesium (1.82 g; 0.075 moles) kept under stirring at 25° C. in ethyl ether (20 ml) was added with ethyl bromide (50 mg). After 15 minutes 1,3—dichloro-4-iodobenzene (13.65 g; 0.05 moles) in ethyl ether (20 ml) was added in about 1 hour at the temperature of 18-22° C., and at the end of the addition the stirring was kept on at 20° C. for further 90 minutes. The metallic magnesium was decanted and the surnatant solution was added in 10 minutes to a suspension of dry zinc chloride (13.6 g; 0.1 mole) in ethyl ether (20 ml). The suspension was stirred at room temperature for 90 minutes, then cooled to 0° C., added with dry DMF (40 ml) then with palladium acetate (168 mg; 0.75 mmoles) and triphenylphosphine (395 mg; 1.5 mmoles) and at last a solution of diethyl iodo-fumarate (10.45 g; 0.035 moles), prepared according to J. Am. Chem. Soc. 1972, 94 (12), 4363-4, in DMF (10 ml) was dropped in about 30 minutes. The mixture was stirred at room temperature overnight, then cooled to 0° C. added with IN HCl (80 ml) and twice extracted with hexane (80 ml) The organic phases were anhydrified over Na2SO4 and evaporated to dryness. The residue (13 g) was purified by flash chromatography (SiO2; hexane/ethyl ether 95/5) to give 7.82 g of pure (E)-2-(2,4-dichlorophenyl)-butendioic acid diethyl ester (yield: 70% calculated with respect to the diethyl iodo-fumarate).
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]([CH3:18])[CH:15]=[CH:14][C:13]=1[OH:19])([O-])=O.NCCCN.O>C1(C)C(C)=CC=CC=1>[OH:19][C:13]1[CH:14]=[CH:15][C:16]([CH3:18])=[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: Cc1ccc(O)c(N=Nc2ccccc2[N+](=O)[O-])c1
Agent: NCCCN
Solvent: O
Solvent: Cc1ccccc1C
Product: Cc1ccc(O)c(-n2nc3ccccc3n2)c1

Procedure:
To a 1000-ml. round-bottomed, three-neck flask fitted with a gas inlet tube, stirrer and reflux condenser is added 20.0 grams (0.08 mol) of 2-nitro-2'-hydroxy-5'-methylazobenzene (99.7% pure) dissolved in a solution of 200 ml of xylene. To this solution is added with stirring a mixture of 23.0 grams (0.32 mol) of 1,3-diaminopropane, 100 ml of water and 4 grams (0.02 mol) of cupric acetate. Carbon monoxide gas is then bubbled through the stirred reaction mixture for 15-20 hours with the temperature being maintained at 85°-90° C.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][C:5]1[N:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=3[C:23]3[N:27]=[N:26][NH:25][N:24]=3)=[CH:15][CH:16]=2)[C:8]([CH2:28][OH:29])=[C:7]([Cl:30])[N:6]=1.[O-]CC.[Mg+2:34].[O-]CC.CCCCCCC>C(O)(C)C>[CH3:1][CH2:2][CH2:3][CH2:4][C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=3[C:23]3[N:27]=[N:26][NH:25][N:24]=3)=[CH:13][CH:12]=2)[C:8]([CH2:28][OH:29])=[C:7]([Cl:30])[N:6]=1.[Mg:34]
Reactant: [Mg+2]
Agent: CCCCc1nc(Cl)c(CO)n1Cc1ccc(-c2ccccc2-c2nn[nH]n2)cc1
Agent: CC[O-]
Solvent: CCCCCCC
Solvent: CC(C)O
Product: [Mg]
Temperature: 25 °C

Procedure:
To 40.81 g of losartan of Example 1 in 235 ml of i-propanol, 6.07 g magnesium ethoxide were added, and stirred at reflux temperature overnight. Reaction mixture was hot filtered, 650 ml n-heptane were added, and cooled to room temperature for the product to precipitate. It was filtered and washed with 110 ml n-heptane, and dried in vacuo at 50° C. to yield 37.9 g losartan magnesium.
Reaction SMILES: [Cl-].[K+].[C:3]([O-:15])(=[O:14])[CH2:4][C:5]([CH2:10][C:11]([O-:13])=[O:12])([C:7]([O-:9])=[O:8])[OH:6].[K+].[K+].[K+].C([O-])(=O)CC(CC([O-])=O)(C([O-])=O)O.[Mg+2:32].C([O-])(=O)CC(CC([O-])=O)(C([O-])=O)O.[Mg+2].[Mg+2].C([O-])(=O)CC(CC([O-])=O)(C([O-])=O)O.[Mg+2].[K+]>>[Mg:32].[C:3]([O-:15])(=[O:14])[CH2:4][C:5]([CH2:10][C:11]([O-:13])=[O:12])([C:7]([O-:9])=[O:8])[OH:6]
Reactant: [Mg+2]
Agent: O=C([O-])CC(O)(CC(=O)[O-])C(=O)[O-]
Agent: [Cl-]
Agent: [K+]
Product: [Mg]

Procedure:
Each patient underwent five phases of study: placebo, potassium chloride, potassium citrate, magnesium citrate, and potassium-magnesium citrate. The results (mean values for the two patients) are outlined in Table 1. Compared to potassium chloride, potassium magnesium citrate gave a higher urinary pH, magnesium, and citrate. Compared to potassium citrate, potassium magnesium citrate produced a greater citrate excretion as well as enhanced magnesium excretion. Compared to magnesium citrate, potassium magnesium citrate gave higher values for urinary pH and citrate. Finally, compared to the placebo, potassium magnesium citrate produced higher values for urinary pH, magnesium, potassium and citrate, and lower values for urinary calcium and oxalate.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH:11]([C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=2[F:28])[C:12]2[N:17]=[CH:16][C:15]([C:18](O)=[O:19])=[CH:14][CH:13]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(N(CC)CC)C.Cl.C(N=C=NCCCN(C)C)C.[O:48]1[CH:52]=[CH:51][CH:50]=[C:49]1[C:53]([NH:55][NH2:56])=[O:54]>CN(C)C1C=CN=CC=1.ClCCl>[O:48]1[CH:52]=[CH:51][CH:50]=[C:49]1[C:53]([NH:55][NH:56][C:18](=[O:19])[C:15]1[CH:14]=[CH:13][C:12]([CH:11]([S:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)(=[O:10])=[O:9])[C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=2[F:28])=[N:17][CH:16]=1)=[O:54]
Reactant: O=C(O)c1ccc(C(c2cc(F)ccc2F)S(=O)(=O)c2ccc(Cl)cc2)nc1
Reactant: NNC(=O)c1ccco1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(NNC(=O)c1ccco1)c1ccc(C(c2cc(F)ccc2F)S(=O)(=O)c2ccc(Cl)cc2)nc1
Temperature: 25 °C
Reaction time: 7.5 h
Yield: 57.9 %

Procedure:
To a dichloromethane (5 ml) solution of the [6-[(4-chlorophenylsulfonyl)(2,5-difluorophenyl)methyl]pyridin-3-yl]carboxylic acid (80 mg, 0.19 mmol) obtained in Example 50 were added triethylamine (32 μl, 0.23 mmol), 4-dimethylaminopyridine (12 mg, 0.095 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (44 mg, 0.23 mmol) and 2-furanhydrazide (29 mg, 0.23 mmol). The resulting mixture was stirred at room temperature for 7.5 hours. The reaction mixture was diluted with dichloromethane. The diluted mixture was then washed sequentially with water, a saturated aqueous solution of sodium bicarbonate and brine. The organic layer thus obtained was dried over magnesium sulfate and concentrated under reduced pressure under reduced pressure. The residue thus obtained was subjected to flash silica gel column chromatography. The fraction obtained from the dichloromethane:methanol=50:1 eluate was concentrated under reduced pressure. The solid thus obtained was recrystallized from dichloromethane-hexane to give the title compound (58 mg, 0.11 mmol, 58%) as a white powder.
Reaction SMILES: C([O-])(=O)C(C)O.[Al+3:7].C([O-])(=O)C(C)O.C([O-])(=O)C(C)O.[OH:20][C:21]1[CH:22]=[CH:23][CH:24]=[C:25]2[C:30]=1[N:29]=[CH:28][CH:27]=[CH:26]2>C(O)C>[CH:23]1[CH:22]=[C:21]([O-:20])[C:30]2[N:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH:24]=1.[CH:23]1[CH:22]=[C:21]([O-:20])[C:30]2[N:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH:24]=1.[CH:23]1[CH:22]=[C:21]([O-:20])[C:30]2[N:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH:24]=1.[Al+3:7]
Reactant: Oc1cccc2cccnc12
Agent: CC(O)C(=O)[O-]
Agent: [Al+3]
Solvent: CCO
Product: [O-]c1cccc2cccnc12

Procedure:
Aluminum lactate, Al[CH3CH(OH)CO2]3, (10.0 g) and 8-hydroxyquinoline (16.0 g) were placed in a 250 mL round bottomed flask equipped with a magnetic stir bar and a reflux condenser. Ethanol (150 mL, denatured) was added and the cream colored slurry was stirred magnetically. The flask was heated to reflux by means of an electric heating mantle and reflux was maintained for 17 hours. Upon initial heating, the cream colored slurry gradually became yellowish in color. The yellow color intensified as the reaction progressed and the reaction mixture remained heterogeneous throughout the reflux period. After cooling, the reaction mixture was filtered and the yellow filter cake was sequentially washed with two 50 mL portions of ethanol, two 50 ml portions of distilled water, two 50 mL portions of ethanol, and two 50 mL portions of diethyl ether. The filter cake was air dried for 24 hours to give 14.9 g of tris(8-quinolinolato)aluminum as a bright yellow powder. The 1H-NMR spectrum of the powder matched that of a commercial sample of tris(8-quinolinolato)aluminum. The powder was dissolved in hot CHCl3 and filtered through a medium porosity glass frit. Addition of heptane and cooling to approximately 0° C. caused fine yellow needles of AlQ to precipitate from the yellow filtrate. the needles were collected by filtration, washed with petroleum ether, vacuum dried, and used to fabricate an electroluminescent lamp.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[Mg+2].[Cl-].[Cl-].[I:15]I>C1COCC1.[NH4+].[Cl-].[O-]S([O-])(=S)=O.[Na+].[Na+]>[F:8][C:6]1[CH:5]=[CH:4][C:3]([N+:9]([O-:11])=[O:10])=[C:2]([F:1])[C:7]=1[I:15]
Reactant: II
Reactant: O=[N+]([O-])c1ccc(F)cc1F
Agent: O=S([O-])([O-])=S
Agent: [Cl-]
Agent: [Mg+2]
Solvent: C1CCOC1
Product: O=[N+]([O-])c1ccc(F)c(I)c1F
Temperature: 25 °C
Reaction time: 8 h
Yield: 73.7 %

Procedure:
A dry, argon-filled Schlenk tube with a magnetic stirrer bar and septum is initially charged with 2,4-difluoro-1-nitrobenzene (159 mg, 1 mmol) in anhydrous THF (2 ml). After adding (TMP)2Zn.MgCl2 (3.00 ml, 1.2 mmol) at 25° C., the mixture is stirred for 30 min, then a solution of iodine (381 mg, 1.5 mmol) in anhydrous THF (2 ml) is added dropwise and the mixture is stirred at 25° C. overnight. For workup, the mixture is diluted with aqueous sat. NH4Cl solution (30 ml) and aqueous sat. Na2S2O3 solution (30 ml) and extracted with ethyl acetate (3×30 ml). After the combined organic phases have been dried over Na2SO4, the solvent has been distilled off and purification has been effected by column chromatography on silica gel (heptane:ethyl acetate), the desired compound (210 mg, 74% of theory) was obtained as a colourless crystalline product.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:17]=[C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:15]([C:26]([CH3:28])=[CH2:27])=[CH:14][C:10]=1[C:11](O)=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.C(N=C=N)C.ON1C2C=CC=CC=2N=N1.Cl.Cl.[CH2:47]1[C:55]2[C:50](=[CH:51][C:52]([C:56]3([OH:63])[CH2:61][CH2:60][N:59]([CH3:62])[CH2:58][CH2:57]3)=[CH:53][CH:54]=2)[CH2:49][NH:48]1.C(N(CC)CC)C>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:17]=[C:16]([O:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:15]([C:26]([CH3:28])=[CH2:27])=[CH:14][C:10]=1[C:11]([N:48]1[CH2:49][C:50]2[C:55](=[CH:54][CH:53]=[C:52]([C:56]3([OH:63])[CH2:61][CH2:60][N:59]([CH3:62])[CH2:58][CH2:57]3)[CH:51]=2)[CH2:47]1)=[O:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C=C(C)c1cc(C(=O)O)c(OCc2ccccc2)cc1OCc1ccccc1
Reactant: CN1CCC(O)(c2ccc3c(c2)CNC3)CC1
Agent: CCN=C=N
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: C=C(C)c1cc(C(=O)N2Cc3ccc(C4(O)CCN(C)CC4)cc3C2)c(OCc2ccccc2)cc1OCc1ccccc1
Reaction time: 0.58 h
Yield: 68.8 %

Procedure:
2,4-Bis-benzyloxy-5-isopropenyl-benzoic acid (1.65 g, 4.4 mmol), 1-[3-(dimethylamino)propyl)]-3-ethylcarbodiimide hydrochloride (843 mg, 4.4 mmol) and 1-hydroxybenztriazole (595 mg, 4.4 mmol) were dissolved in DMF (20 mL). After 35 minutes, the solution was added to a suspension of 4-(2,3-dihydro-1H-isoindol-5-yl)-1-methyl-piperidin-4-ol dihydrochloride (1.22 g, 4.0 mmol) in DMF (5 mL) and triethylamine (1.4 mL, 10 mmol). The mixture was stirred for 3 hours then concentrated in vacuo. The residue was taken up in ethyl acetate and washed with a mixture of water (adjusted to pH 14 with 2N sodium hydroxide solution) and brine. The aqueous phase was extracted twice further with ethyl acetate then the combined organic extracts were washed with sodium bicarbonate solution and brine, dried (MgSO4) and concentrated. The crude product was purified by flash chromatography (gradient elution with 2M methanolic ammonia/dichloromethane, 2% to 10%) to afford the title compound as a brown foam (1.62 g, 69%). 1H NMR (methanol-d4) 7.51-7.14 (14H, m), 6.85 (0.5H, s), 6.84 (0.5H, s), 5.16 (2H, s), 5.15 (2H, s), 5.10-5.08 (1H, m), 5.07-5.05 (1H, m), 4.87 (1H, s), 4.86 (1H, s), 4.61 (2H, br.s), 2.78-2.70 (2H, m), 2.57 (1H, td), 2.54 (1H, td), 2.36 (1.5H, s), 2.34 (1.5H, s), 2.16-2.05 (5H, m including 2.09 (3H, s)), 1.78-1.70 (2H, m). MS: [M+H]+ 589.
Reaction SMILES: [CH3:1][C:2]1([CH3:9])[CH2:6][O:5][C:4](=[O:7])[C:3]1=[O:8].O=O.[H][H]>C1(C)C=CC=CC=1>[OH:8][CH:3]1[C:2]([CH3:9])([CH3:1])[CH2:6][O:5][C:4]1=[O:7]
Reactant: [H][H]
Reactant: CC1(C)COC(=O)C1=O
Agent: O=O
Solvent: Cc1ccccc1
Product: CC1(C)COC(=O)C1O
Temperature: 40 °C

Procedure:
200 g (1.561 mol) of dihydro-4,4-dimethyl-2,3-furandione (ketopantolactone) and 600 ml of toluene were placed in a 1 liter stirring autoclave. After heating to 40° C. the air was removed from the autoclave by evacuation 5 times with a high vacuum pump (0.05-0.1 bar) and gasification with 10 bar of hydrogen each time. The temperature of the ketopantolactone solution was then adjusted to 35° C., the pressure was lowered to 0.5 bar and immediately 50 ml of the catalyst solution prepared in accordance with Example 1 were sucked in with the complete absence of O2. After pressurizing to 40 bar of hydrogen the mixture was hydrogented while stirring and at constant pressure (40 bar) at 35° C. for 1 hour and at 45° C. for 4 hours. After a total hydrogenation time of 5 hours the pale yellow hydrogenation solution was removed under pressure from the autoclave and the autoclave was subsequently rinsed 3 times with 100 ml of toluene each time. The combined toluene solutions were evaporated on a rotary evaporator at 60° C./17 mbar. The residue (210 g) was distilled at 130°-150° C. bath temperature and 12 mbar. There were obtained 201.6 g (99.3%) of R-(α-hydroxy-β,β-dimethyl-γ-butyrolactone (=R-(-)-pantolactone) with an optical purity of 90.7%. [α]D20 =-46.8° (c=3 in H2O).
Reaction SMILES: [N+:1]([CH:4]=[C:5](SC)[NH:6][CH2:7][CH2:8][S:9][CH2:10][C:11]1[NH:15][CH:14]=[N:13][C:12]=1[CH3:16])([O-:3])=[O:2].[NH2:19][CH2:20][CH2:21][S:22][CH2:23][C:24]1[S:25][CH:26]=[CH:27][N:28]=1>>[N+:1]([CH:4]=[C:5]([NH:6][CH2:7][CH2:8][S:9][CH2:10][C:11]1[NH:15][CH:14]=[N:13][C:12]=1[CH3:16])[NH:19][CH2:20][CH2:21][S:22][CH2:23][C:24]1[S:25][CH:26]=[CH:27][N:28]=1)([O-:3])=[O:2]
Reactant: CSC(=C[N+](=O)[O-])NCCSCc1[nH]cnc1C
Reactant: NCCSCc1nccs1
Product: Cc1nc[nH]c1CSCCNC(=C[N+](=O)[O-])NCCSCc1nccs1

Procedure:
Reaction of 1-nitro-2-methylthio-2-[2-((4-methyl-5-imidazolyl)methylthio)ethylamino]ethylene with an excess of 2-[(2-aminoethyl)thiomethyl]thiazole according to the procedure of Example 2 (ii) results in the production of 1-nitro-2-[2-((4-methyl-5-imidazolyl)methylthio)ethylamino]-2-[2-(2-thiazolylmethylthio)ethylamino]ethylene.
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[Cl:12][CH2:13][C:14](Cl)=[O:15]>C1(C)C=CC=CC=1>[Cl:11][C:8]1[CH:9]=[CH:10][C:2]([NH:1][C:14](=[O:15])[CH2:13][Cl:12])=[C:3]([CH:7]=1)[C:4]([OH:6])=[O:5]
Reactant: Nc1ccc(Cl)cc1C(=O)O
Reactant: O=C(Cl)CCl
Solvent: Cc1ccccc1
Product: O=C(CCl)Nc1ccc(Cl)cc1C(=O)O
Yield: 95.6 %

Procedure:
3.0 g (17.5 mmol) of 2-amino-5-chlorobenzoic acid and 3.95 g (35.0 mmol) of chloroacetyl chloride were heated under reflux in 60 mL of toluene for 1 hour. Thereafter, the solvent was distilled off under reduced pressure, and H2O was added to the resulting residue. Solids were collected by filtration to give 4.15 g of 5-chloro-2-[(chloroacetyl)amino]benzoic acid (yield: 96%).
Reaction SMILES: C([O-])(=O)C.C([O-])(=O)C.C([Sn+2]CCCC)CCC.[CH3:18][CH:19]([O:22][C:23]1[CH:32]=[CH:31][C:26]([O:27][CH2:28][CH2:29][OH:30])=[CH:25][CH:24]=1)[CH2:20][CH3:21].[CH2:33]([N:35]=[C:36]=[O:37])[CH3:34].CCOCC>CN(C=O)C.O>[CH2:33]([NH:35][C:36](=[O:37])[O:30][CH2:29][CH2:28][O:27][C:26]1[CH:31]=[CH:32][C:23]([O:22][CH:19]([CH3:18])[CH2:20][CH3:21])=[CH:24][CH:25]=1)[CH3:34]
Reactant: CCN=C=O
Reactant: CCC(C)Oc1ccc(OCCO)cc1
Agent: CC(=O)[O-]
Agent: CCCC[Sn+2]CCCC
Solvent: CCOCC
Solvent: O
Solvent: CN(C)C=O
Product: CCNC(=O)OCCOc1ccc(OC(C)CC)cc1
Temperature: 25 °C

Procedure:
Dibutyltin diacetate (0.004 ml) is added to a solution of the above alcohol (0.42 g, 2.0 mmol) in 1.5 ml of DMF and the mixture is chilled in an ice bath. Ethyl isocyanate (0.18 ml, 2.2 mmol) is then added and the mixture is allowed to warm slowly to RT. The mixture is then poured into ether and water containing 10% potassium dihydrogen phosphate. The aqueous phase is extracted with ether, and the combined organic phases are washed with water and with brine, dried, filtered and the solvent is removed in vacuo to give O-2-[4-(1-methylpropoxy)phenoxy]ethyl N-ethylcarbamate (compound 30, Table A).
Reaction SMILES: [O:1]=[C:2]1[C:7]2[N:8]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=3[C:6]=2[O:5][C:4]([C:21]([O:23]CC)=[O:22])=[CH:3]1.O>C(O)(=O)C.Cl>[O:1]=[C:2]1[C:7]2[N:8]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=3[C:6]=2[O:5][C:4]([C:21]([OH:23])=[O:22])=[CH:3]1
Reactant: CCOC(=O)c1cc(=O)c2c(o1)c1ccccc1n2-c1ccccc1
Agent: Cl
Solvent: CC(=O)O
Solvent: O
Product: O=C(O)c1cc(=O)c2c(o1)c1ccccc1n2-c1ccccc1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
A mixture of 1.0 g (0.0033 mole) of ethyl 4,5-dihydro-4-oxo-5-phenylpyrano[3,2-b]indole-2-carboxylate in 10 ml glacial acetic acid and 2.0 ml conc. hydrochloric acid was stirred at reflux for 41/2 hr, then cooled and added to 75 g ice--H2O. The solid was filtered, washed with cold water, then added to a mixture of 35 ml 5% aqueous sodium carbonate and 250 ml water. After filtering by gravity, the aqueous solution was washed three times with 75 ml chloroform, cooled in ice, and acidified with 4.0 N hydrochloric acid. The orange precipitate was filtered, digested 15 min on the steam bath with 25 ml water and re-filtered warm. Recrystallization from DMF-water yielded an off-white solid of mpt. >290°.
Reaction SMILES: [NH2:1][CH2:2][C:3]1([CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH:8]2[CH:4]1[CH:5]=[C:6]([CH2:10][CH3:11])[CH2:7]2.O.[C:21]1([CH3:31])[CH:26]=[CH:25][C:24]([S:27]([OH:30])(=[O:29])=[O:28])=[CH:23][CH:22]=1>C(OCC)(=O)C>[C:21]1([CH3:31])[CH:22]=[CH:23][C:24]([S:27]([OH:30])(=[O:28])=[O:29])=[CH:25][CH:26]=1.[NH2:1][CH2:2][C@:3]1([CH2:12][C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH2:9][C@@H:8]2[C@H:4]1[CH:5]=[C:6]([CH2:10][CH3:11])[CH2:7]2
Reactant: CCC1=CC2C(C1)CC2(CN)CC(=O)OC(C)(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCOC(C)=O
Solvent: O
Product: CCC1=C[C@@H]2[C@H](C1)C[C@]2(CN)CC(=O)OC(C)(C)C
Temperature: 25 °C
Yield: 80.6 %

Procedure:
Ethyl acetate (70 ml, 10.4 v/w) was added to tert-butyl [6-aminomethyl-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetate (7.8 g, purity: 86.7%, 22.03 mmol, 87:13 diastereomeric mixture), and the mixture was stirred at room temperature. After addition of p-toluenesulfonic acid monohydrate (4.2 g, 22.03 mmol, 0.87 eq.), the mixture was stirred at room temperature for 3 hours, and a crystal was collected by filtration. Then, the crystal was dried under reduced pressure under the condition of 40° C. to obtain tert-butyl [(1R*,5S*,6S*)-6-aminomethyl-3-ethylbicyclo[3.2.0]hept-3-en-6-yl]acetate p-toluenesulfonate as a white crystal (7.8 g, yield: 80.6%, diastereomeric ratio: 99.7:0.3).
Reaction SMILES: [Sb:1](=O)([O-])([O-])[O-].[Na+].[Na+].[Na+].[Sb].[C:10]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])(=[O:13])[CH2:11][SH:12].Cl>O>[C:10]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])(=[O:13])[CH2:11][SH:12].[Sb+5:1]
Reactant: O=[Sb]([O-])([O-])[O-]
Agent: CCCCCCOC(=O)CS
Agent: Cl
Agent: [Na+]
Solvent: O
Product: [Sb+5]
Reaction time: 2 h

Procedure:
Sodium antimonate obtained from U.S. Antimony Corporation (22.73 g, 0.0563 mole) was placed in the reaction vessel and the hexyl thioglycolate (100 ml, 0.5625 mole) added and stirred. Concentrated hydrochloric acid from Fisher Scientic Co. (9.52 ml, 0.1125 mole) was added dropwise, and an immediate temperature rise of 12° C. occurred. The mixture was thereafter heated and the byproduct of the reaction, water, was distilled over at 96° C. and collected. After 2 hours, a 92% yield of antimony (V) hexyl thioglycolate was obtained. The product was filtered to remove unreacted sodium antimonate and the additional byproduct of the reaction, sodium chloride.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[N:3]=1.Br[N:10]1[C:14](=O)CC[C:11]1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][N:10]([CH3:14])[CH3:11])[N:3]=1
Reactant: Cc1cccc(Cl)n1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CN(C)Cc1cccc(Cl)n1

Procedure:
2-Chloro-6-methylpyridine (6.4 g, 0.05 mol) is refluxed with N-bromosuccinimide (8.9 g, 0.05 mol) in 50 ml of carbon tetrachloride with benzoyl peroxide (50 mg) until the N-bromosuccinimide has reacted completely (7-14 hours). The succinimide is removed by filtering and the filtrate is saturated with anhydrous dimethylamine. Dimethylamine hydrochloride is removed by filtration and the filtrate is concentrated in vacuo. The residual oil is taken up in hexane and extracted into dilute hydrochloric acid. After the acid extract is washed with ether it is made basic with sodium hydroxide and extracted with ether. The ether extract is dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. This gives 2.2 g of 2-chloro-6-dimethylaminomethylpyridine as a pale yellow oil.