Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[O:21])[CH:10]([CH2:19][CH3:20])[C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1.C1(C(CC2C=CC(OC)=CC=2)=O)C=CC(OC)=CC=1.C(Br)C.[Li+].CC([N-]C(C)C)C.Br[CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH:63]([CH:65]1[CH2:70][CH2:69][CH2:68][CH2:67][O:66]1)[OH:64].[Mg].Cl>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]([OH:21])([CH:10]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[CH2:19][CH3:20])[CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH:63]([CH:65]2[CH2:70][CH2:69][CH2:68][CH2:67][O:66]2)[OH:64])=[CH:7][CH:8]=1
Reactant: CCC(C(=O)c1ccc(OC)cc1)c1ccc(OC)cc1
Reactant: OC(CCCCCCCCCCBr)C1CCCCO1
Agent: CC(C)[N-]C(C)C
Agent: COc1ccc(CC(=O)c2ccc(OC)cc2)cc1
Agent: Cl
Solvent: C1CCOC1
Solvent: CCBr
Product: CCC(c1ccc(OC)cc1)C(O)(CCCCCCCCCCC(O)C1CCCCO1)c1ccc(OC)cc1
Reaction time: 18 h
Yield: 76 %

Procedure:
4'-methoxy-2-ethyl,2-(4methoxyphenyl)acetophenone (2) (710 mg, 2.5 mmol, prepared from desoxyanisoin, ethyl bromide and LDA by a known method) in THF (10 ml) were added, under argon, to Grignard reagent prepared from 11-bromo-tetrahydropyranyl undecanol (6.6 g, 19.7 mmoles) and magnesium (0.6 g, 24.7 mmoles) and THF (10 ml). The mixture was stirred for 18 hours, then acidified with 1N HCl and extracted three times with ether. The organic phase was washed with water (X3), dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was chromatographed on Silica-gel (Kieselgel, 60F254, Merck, 0.063-0.200 mm, 100 g). Elution with a mixture of hexane-ethyl acetate (9:1 v/v) gave 12,13-Bis-(4-methoxyphenyl)tetrahydropyranyl pentadecan-1,12-diol (991 mg, 76%) as a mixture of diastereoisomers; colorless oil, IR νmax (neat) 3480, 1600 cm-1 ; 1H-NMR (δ, CDCl3); 0.62 (3H, t, J=7.3 Hz, CH2CH3), 2.73 (1H, 2d, J=9.7 Hz, --CHCH2CH3), 3.25-4.00 (4H, m, --CH2OCHOCH2 --), 3.76 and 3.79 (6H, 2s, --OCH3), 4.57 (1H, t, J=1.1 Hz, --O2 --CH--CH2) and 6.71-7.30 (8H, m, H--Ar)ppm. MS m/e=523 (M+ --H2O).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([C:13]1[CH:18]=[CH:17][C:16]([C:19]([CH3:22])([CH3:21])[CH3:20])=[CH:15][CH:14]=1)[N:8]=[CH:7]2.[N:23]1[CH:28]=[CH:27][C:26]([CH:29]=O)=[CH:25][CH:24]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].S(NN)(C1C=CC(C)=CC=1)(=O)=O>C(Cl)Cl>[C:19]([C:16]1[CH:15]=[CH:14][C:13]([N:9]2[N:8]=[CH:7][C:6]3[C:11](=[C:2]([NH:1][CH2:29][C:26]4[CH:27]=[CH:28][N:23]=[CH:24][CH:25]=4)[CH:3]=[CH:4][CH:5]=3)[C:10]2=[O:12])=[CH:18][CH:17]=1)([CH3:22])([CH3:21])[CH3:20]
Reactant: O=Cc1ccncc1
Reactant: CC(C)(C)c1ccc(-n2ncc3cccc(N)c3c2=O)cc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cc1ccc(S(=O)(=O)NN)cc1
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)(C)c1ccc(-n2ncc3cccc(NCc4ccncc4)c3c2=O)cc1
Temperature: 25 °C
Reaction time: 7 h

Procedure:
To a solution of the amine (Step E, 45 mg, 0.15 mmol) and CH2Cl2 (10 mL) was added 4-pyridinecarboxaldehyde (0.04 mL, 0.39 mmol) and NaBH(OAc)3 (95 mg, 0.45 mmol). The reaction was stirred at RT for 7 h then quenched with H2O and extracted with CH2Cl2. The organic layer was washed with H2O and brine, dried (MgSO4) and concentrated in vacuo to give the crude product as an orange oil. The crude product was dissolved in 10 mL CH2Cl2 and stirred with PS-TsNHNH2 resin to remove un-reacted aldehyde. After 1 h, the mixture was filtered through Celite® and concentrated in vacuo. The residue was purified by silica flash chromatography (20-75% EtOAc:hexane) to give the desired product as a light-yellow crystalline solid. MS m/e 385 (M+H)+. Calc'd for C24H24N4O-384.47.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([F:16])=[CH:11][C:10]=1[N+:17]([O-])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>[Pt].C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([F:16])=[CH:11][C:10]=1[NH2:17])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=[N+]([O-])c1cc(F)c(F)cc1OCc1ccccc1
Agent: [Pt]
Solvent: CCOC(C)=O
Product: Nc1cc(F)c(F)cc1OCc1ccccc1
Reaction time: 6 h

Procedure:
A mixture of 2-benzyloxy-4,5-difluoronitrobenzene (2.35 g, 8.86 mmol) and 10% platinum on carbon (235 mg) in ethyl acetate (50 mL) is hydrogenated at atmospheric pressure for 6 h. The catalyst is filtered through Celite and solvent removed under reduced pressure. The residue is purified by silica gel chromatography on an Isco Companion using a gradient of 90:10 to 50:50 hexane/ethyl acetate to afford the title compound. 1H NMR (δ, CDCl3): 7.39 (m, 5H), 6.68 (dd, 1H, J=11.6, 7.3 Hz), 6.52 (dd, 1H, J=11.6, 7.8 Hz), 5.01 (s, 2H), 3.74 (br s, 2H). MS (M+1): 236.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:14][CH2:13][C:12](=[O:15])[CH2:11][CH2:10]1.C(O)C.[BH4-].[Na+].Cl>C(OCC)(=O)C>[OH:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[C@H:9]1[CH2:14][CH2:13][C@H:12]([OH:15])[CH2:11][CH2:10]1
Reactant: O=C1CCC(c2ccc(O)cc2O)CC1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: CCOC(C)=O
Product: Oc1ccc([C@H]2CC[C@H](O)CC2)c(O)c1
Reaction time: 16 h

Procedure:
4-(2,4-Dihydroxyphenyl)cyclohexanone (18 mg) was placed in a round-bottomed flask equipped with magnetic stirrer. Ethanol (5 ml) was added, followed by sodium borohydride (3.3 mg), and the reaction mixture was stirred for 16 hr. Aqueous HCl (20 ml, 1M), followed by ethyl acetate (20 ml), was added, and the organic phase removed and washed with brine (15 ml), dried over anhydrous magnesium sulphate, filtered, and then concentrated in vacuo. The residue was purified by flash column chromatography (SiO2, ethyl acetate/petroleum ether, 60:40, v/v) to afford the title compound (14 mg, 78%) as a white solid. δH(CD3OD) 1.38-1.56 (4H, m), 1.85-1.88 (2H, m), 2.04-2.07 (2H, m), 2.80 (1H, tt), 3.58-3.65 (1H, m), 6.24-6.29 (2H, m), 6.90 (1H, d); m/z (ES−) 267 ((M+AcOH)−1)
Reaction SMILES: [CH2:1]([N:12]([CH2:17][C:18]([O-:20])=[O:19])[CH2:13][C:14]([OH:16])=[O:15])[CH2:2][N:3]([CH2:8][C:9]([O-:11])=[O:10])[CH2:4][C:5]([OH:7])=[O:6].[Na+].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>[Ag]>[CH2:2]([N:3]([CH2:8][C:9]([OH:11])=[O:10])[CH2:4][C:5]([OH:7])=[O:6])[CH2:1][N:12]([CH2:17][C:18]([OH:20])=[O:19])[CH2:13][C:14]([OH:16])=[O:15]
Reactant: O=C([O-])CN(CCN(CC(=O)[O-])CC(=O)O)CC(=O)O
Agent: [Ag]
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: O=C(O)CN(CCN(CC(=O)O)CC(=O)O)CC(=O)O

Procedure:
An EA-5 fixer solution is treated in the silver recovery unit 200 shown in FIG. 2 which also incorporates a silver precipitating unit 80, according to U.S. Pat. No. 5,437,792 and described above. Silver precipitating unit 80 comprises a vessel 81 which receives untreated EA-5 fixer via line 250 at inlet 49 and is drawn via line 220 at outlet 39 to form a continuous stream of untreated EA-5 fixer flowing at a rate of 100 mls/minute. A solution of 15 g/l disodium EDTA dihydrate and 45 g/l sodium carbonate in storage vessel 210 is drawn off by line 211 by pump 212. The solution is then pumped to line 220 via line 213 and injected at a rate of 100 mls per minute through injection tee 215 into a seasoned and untreated EA-5 fixer solution with a pH of about 4.1, in line 220, flowing at a rate of 100 mls per minute. The resulting solution is then mixed within a tubular reactor 216. The solution is then returned to a silver precipitation unit 80 which employs TMT as a silver precipitating agent, and a flocculant to agglomerate the TMT-silver precipitate, as described above.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[C:4]([I:11])[CH:3]=1.B.C1COCC1.O>C1COCC1>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([CH2:6][OH:7])=[C:4]([I:11])[CH:3]=1
Reactant: O=C(O)c1ccc(Cl)cc1I
Agent: B
Solvent: O
Solvent: C1CCOC1
Product: OCc1ccc(Cl)cc1I
Temperature: 0 °C
Reaction time: 8 h

Procedure:
4-Chloro-2-iodobenzoic acid (5.0 g, 18 mmol) was dissolved in THF (40 mL) and cooled to 0° C. Borane-THF complex (1M in THF) (35 mL, 35 mmol) was added by syringe. The solution was allowed to warm to room temperature and stirred overnight. The reaction was monitored by LCMS and TLC. When the reaction was complete, water was added until gas evolution ceased and then the THF was removed under vacuum. EtOAc (100 mL) was added, and the organic layer was washed with water (3×50 mL), brine (3×50 mL), dried with MgSO4, and concentrated in vacuo resulting in a white solid.
Reaction SMILES: [N:1]([C:4]1[C:8]([CH3:9])=[CH:7][S:6][CH:5]=1)=[C:2]=[S:3].[O:10]1[C:14]2([CH2:19][CH2:18][CH2:17][CH2:16][CH:15]2[NH2:20])[O:13][CH2:12][CH2:11]1>O1CCCC1>[O:10]1[C:14]2([CH2:19][CH2:18][CH2:17][CH2:16][CH:15]2[NH:20][C:2]([NH:1][C:4]2[C:8]([CH3:9])=[CH:7][S:6][CH:5]=2)=[S:3])[O:13][CH2:12][CH2:11]1
Reactant: Cc1cscc1N=C=S
Reactant: NC1CCCCC12OCCO2
Solvent: C1CCOC1
Product: Cc1cscc1NC(=S)NC1CCCCC12OCCO2
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 3-isothiocyanato-4-methylthiophene (296.2 mg, see example 1a) in absolute tetrahydrofuran (10 ml) was added dropwise to a solution of 1,4-dioxaspiro[4.5]dec-6-ylamine (300 mg) in absolute tetrahydrofuran (10 ml), the mixture was stirred at room temperature for 2 hours and the solvent was then removed under reduced pressure. The residue was purified by preparative chromatography and the product-containing fractions were combined, freed from acetonitrile, made basic and extracted three times with ethyl acetate. The organic phases were combined, dried (MgSO4) and filtered. This gave 428 mg of the desired product.
Reaction SMILES: Br[CH2:2][C:3]([C@:5]1([OH:27])[CH2:22][C:21]2[C:20]([OH:23])=[C:19]3[C:10]([C:11](=[O:25])[C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=4[C:18]3=[O:24])=[C:9]([OH:26])[C:8]=2[CH2:7][CH2:6]1)=[O:4].[Na]>CC(C)=O>[CH2:3]([O:4][CH2:2][C:3]([C@:5]1([OH:27])[CH2:22][C:21]2[C:20]([OH:23])=[C:19]3[C:10]([C:11](=[O:25])[C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=4[C:18]3=[O:24])=[C:9]([OH:26])[C:8]=2[CH2:7][CH2:6]1)=[O:4])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:21][CH2:20][CH3:19]
Reactant: O=C1c2ccccc2C(=O)c2c(O)c3c(c(O)c21)CC[C@](O)(C(=O)CBr)C3
Agent: [Na]
Solvent: CC(C)=O
Product: CCCCCCCCOCC(=O)[C@@]1(O)CCc2c(O)c3c(c(O)c2C1)C(=O)c1ccccc1C3=O
Temperature: 25 °C

Procedure:
A mixture of 9(R)-bromoacetyl-6,9,11-trihydroxy-5,7,8,9,10,12-hexahydronaphthacene-5,12-dione (1.00 g) obtained in Reference Example 4-(1), sodium octate (4.8 g) and acetone (50 ml) was stirred under reflux for 3 hours, cooled to room temperature and concentrated under reduced pressure. The residue was triturated with addition of ether (15 ml). Solid substances were filtered to give orange crystals of 9(R)-octyloxyacetyl-6,9,11-trihydroxy-5,7,8,9,10,12-hexahydronaphthacene-5,12-dione. M.P., 144°-148° C.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[C:9]([SH:11])[CH:8]=[C:7]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:6]=1[OH:16])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:24][Si:25]([CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])([CH3:27])[CH3:26].Cl>CN(C)C=O>[C:12]([C:7]1[CH:8]=[C:9]([S:11][CH2:24][Si:25]([CH3:26])([CH3:27])[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])[CH:10]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[C:6]=1[OH:16])([CH3:15])([CH3:14])[CH3:13]
Reactant: CC(C)(C)c1cc(S)cc(C(C)(C)C)c1O
Reactant: CCCCCCCCCCCC[Si](C)(C)CCl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCCCCCCCCC[Si](C)(C)CSc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Mix 2,6-di-t-butyl-4-mercaptophenol (2.4 g, 10 mmol), potassium carbonate (1.7 g, 12.3 mmol), chloromethyldodecyldimethylsilane (2.8 g, 10 mmole) and dimethylformamide (50 mL) and stir overnight at room temperature under argon atmosphere. Dilute the mixture with ice-water, acidify with aqueous hydrochloric acid and extract with ethyl ether. Wash the ethereal layer with water, then brine, filter through fluorosil-Na2SO4 and evaporate to an orange semi-solid (4.0 g). Purify the product by first distilling (180-200° C. @ 0.1 mm Hg) then subjecting to silica gel chromatography (CCl4) to obtain the title compound as a colorless oil which slowly crystallizes.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13](O)=O)=[CH:11][C:10]=1[O:18][CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(C=O)C.S(Cl)(Cl)=O.[NH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[SH:36]>C(Cl)Cl.N1C=CC=CC=1.O.C1(C)C=CC=CC=1>[CH2:1]([O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]2[S:36][C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=3[N:29]=2)=[CH:11][C:10]=1[O:18][CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1cc(C(=O)O)ccc1OCc1ccccc1
Reactant: Nc1ccccc1S
Solvent: c1ccncc1
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: COc1cc(-c2nc3ccccc3s2)ccc1OCc1ccccc1
Temperature: 50 °C
Reaction time: 2 h

Procedure:
In methylene chloride (10 ml) was suspended 2.0 g (7.7 mmol) of 4-benzyloxy-3-methoxy benzoic acid. To this suspension was added 0.05 g of DMF and 0.68 ml of thionyl chloride, followed by stirring at 50° C. for 2 hours. This reaction solution was introduced dropwise at 0° C. into a solution wherein 1.2 g (9.3 mmol) of 2-aminothiophenol had been dissolved in 10 ml of pyridine at room temperature. The mixture was further stirred overnight at room temperature, diluted with water, and subjected to ethyl acetate extraction (50 ml×2 times). The extracts were dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue thus obtained was dissolved in 30 ml of toluene. This toluene solution was heated to reflux overnight while water was distilled off. Toluene was removed from this solution by distillation under reduced pressure, and the residue was purified using a silica gel column (eluant:ethyl acetate/hexane=1/5). The solvent was distilled off under reduced pressure. Using the crystals thus obtained, the desired compound was recrystallized in an amount of 0.18 g from methylene chloride-hexane.
Reaction SMILES: [NH2:1][C:2]1[C:7]([S:8]([NH:11][C:12](=O)[CH3:13])(=[O:10])=[O:9])=[CH:6][N:5]=[C:4]([Cl:15])[CH:3]=1.C>C([O-])(O)=O.[Na+]>[Cl:15][C:4]1[N:5]=[CH:6][C:7]2[S:8](=[O:10])(=[O:9])[N:11]=[C:12]([CH3:13])[NH:1][C:2]=2[CH:3]=1
Reactant: CC(=O)NS(=O)(=O)c1cnc(Cl)cc1N
Agent: O=C([O-])O
Agent: [Na+]
Product: CC1=NS(=O)(=O)c2cnc(Cl)cc2N1

Procedure:
0.2 g of 4-amino-5-acetylaminosulfonyl-2- chloropyridine (Preparation 19) is introduced into an open round-bottomed flask placed on an oil bath at 240° C. The temperature of the oil bath is brought over a period of a half-hour from 240° C. to 270° C. The molten mass is then cooled. It is dissolved in 4 cm3 of a tepid NaHCO3 solution (2% m/v). The solution is decolored with absorbing charcoal, filtered and then adjusted to a pH of 4 using formic acid. The crystalline precipitate obtained is collected on a filter, washed with water and dried.
Reaction SMILES: [OH:1][C@@H:2]([CH3:10])[CH:3](Cl)[C:4]([O:6][CH2:7][CH3:8])=[O:5].[Na+].[I-:12]>CC(C)=O>[OH:1][C@H:2]([CH2:10][I:12])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5]
Reactant: CCOC(=O)C(Cl)[C@H](C)O
Reactant: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Product: CCOC(=O)C[C@H](O)CI
Temperature: 59 °C
Reaction time: 120 h
Yield: 95.9 %

Procedure:
To a solution of ethyl 3(S)-hydroxy-chlorobutyrate (1) (639.0 g, 3.84 mol) in dry acetone (7.7 L) is added anhydrous NaI (2300 g, 15.34 mol). The mixture is stirred vigorously at 58-60° C. for 120 hours under argon atmosphere. The acetone is distilled off under the reduced pressure at 40-60° C. The residue is diluted with water (5.75 L) followed by the addition of saturated Na2S2O3 solution (1.53 L) and t-BuMeO (2.3 L). The mixture is stirred vigorously at ambient temperature for 30 minutes. Then the organic layer is separated and the water phase is extracted additionally with t-BuMeO (2×1.15 L). The combined organic layers are washed with water (800 mL) and dried (MgSO4). Evaporation of the solvent under the reduced pressure (20 mbar) at 40° C. affords 949.9 g (96%) of ethyl 3(S)-hydroxy-4-iodobutyrate (2) as yellow oil (GC purity 85.9%). A product with GC purity of 98-99% can be obtained by vacuum distillation (73-89° C. at 0.180-0.330 mbar) of the crude product. 1H NMR (300 MHz, CDCl3): δ 4.17 (q, J=7.2 Hz, 2H), 3.99 (m, 1H), 3.34 (dd, J=10.3 and 5.2 Hz, 1H), 3.28 (dd, J=10.3 and 5.7 Hz, 1H), 3.21 (br s, 1H), 2.67 (dd, J=16.5 and 4.3 Hz, 1H), 2.58 (dd, J=16.5 and 7.9 Hz, 1H), 1.27 (t, J=7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3): δ 171.7, 67.4, 61.0, 40.7, 14.1, 12.0.
Reaction SMILES: [C:1]([O:4][C:5](=[O:7])[CH3:6])(=O)[CH3:2].OC1C=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][CH:10]=1>S(=O)(=O)(O)O>[C:5]([O:4][C:1]1[CH:10]=[CH:11][C:12]([C:13]([OH:15])=[O:14])=[CH:16][CH:2]=1)(=[O:7])[CH3:6]
Reactant: CC(=O)OC(C)=O
Reactant: O=C(O)c1ccc(O)cc1
Agent: O=S(=O)(O)O
Product: CC(=O)Oc1ccc(C(=O)O)cc1
Temperature: 15 °C

Procedure:
For example, 500 grams of acetic anhydride and 2 drops of sulfuric acid are placed in a vessel and 274 grams of p-hydroxy benzoic acid are added with stirring. The contents of the vessel are stirred at 100°C. for 1 hour, and are cooled to about 15°C. The p-acetoxy benzoic acid formed is recovered by pouring the hot acetic anhydride solution over an ice/water mixture, removing the product by filtration, washing the same with deionized water in a high shear mixer, and drying in a forced air oven. A like quantity of m-acetoxy benzoic acid is formed in an identical manner utilizing m-hydroxy benzoic acid as one of the reactants.
Reaction SMILES: C([O-])(C)C.[Mg+2:5].C([O-])(C)C.[Mg].[CH2:11]([OH:21])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]>C(O[Ti](OCCCC)(OCCCC)OCCCC)CCC.C(O)(C)C>[CH2:11]([O-:21])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].[CH2:11]([O-:21])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].[Mg+2:5]
Reactant: CCCCCCCCCCO
Agent: CCCCO[Ti](OCCCC)(OCCCC)OCCCC
Agent: CC(C)[O-]
Agent: [Mg+2]
Solvent: CC(C)O
Product: CCCCCCCCCC[O-]

Procedure:
If magnesium isopropanolate, together with e.g., 20 moles % of tetrabutoxy titanium, with respect to the amount of magnesium, and one or two equivalents of decanol, is introduced into an organic solvent, and the mixture is heated, a desirably low-viscosity solution of magnesium isopropanolatedecanolate, and/or of magnesium didecanolate, is formed, from which the liberated isopropanol can now readily be evaporated so as to achieve substantially full completion of the reaction.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([N:8]2[CH2:17][CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([Cl:18])[CH:14]=3)[C:9]2=[O:19])[CH:5]=[N:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].[NH:26]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[N:27]1.O>O1CCOCC1.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>[Cl:18][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:19])[N:8]([C:4]1[CH:5]=[N:6][CH:7]=[C:2]([C:29]3[CH:30]=[N:26][NH:27][CH:28]=3)[CH:3]=1)[CH2:17][CH2:16]2
Reactant: O=C1c2ccc(Cl)cc2CCN1c1cncc(Br)c1
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: O=C1c2ccc(Cl)cc2CCN1c1cncc(-c2cn[nH]c2)c1
Yield: 27.7 %

Procedure:
2-(5-Bromo-pyridin-3-yl)-6-chloro-3,4-dihydro-2H-isoquinolin-1-one (example 7) (34 mg, 0.1 mmol), Pd(PPh3)4 (5.8 mg, 0.005 mmol), K2CO3 (27.6 mg, 0.2 mmol) and 1H-pyrazole-4-boronic acid pinacol ester (29.1 mg, 0.15 mmol) were dissolved in dioxane (1 mL). The resulting reaction mixture was subject to microwave reaction at 150° C. for 45 min before it was poured into H2O (25 mL) and extracted with EtOAc (2×25 mL). The combined organic layers were washed with brine, dried over anhy. Na2SO4, filtered and concentrated in vacuo to give a crude product which was then purified by prep-HPLC to give title compound (9 mg, 28%) as a white solid. MS: 325.1 (M+H+).
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[C:15]3[C:10](=[N:11][CH:12]=[C:13]([OH:16])[CH:14]=3)[N:9]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH:8]=2)[CH:4]=[N:3]1.Br[CH2:26][CH2:27][CH2:28][CH2:29][CH3:30].C([O-])([O-])=O.[K+].[K+]>[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].CC(C)=O>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[C:15]3[C:10](=[N:11][CH:12]=[C:13]([O:16][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[CH:14]=3)[N:9]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[CH:8]=2)[CH:4]=[N:3]1
Reactant: CCCCCBr
Reactant: Cn1cc(-c2cn(COCC[Si](C)(C)C)c3ncc(O)cc23)cn1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: CC(C)=O
Product: CCCCCOc1cnc2c(c1)c(-c1cnn(C)c1)cn2COCC[Si](C)(C)C
Yield: 52.7 %

Procedure:
According to the general procedure using: 27 (60 mg, 0.174 mmol), 1-bromopentane(129 μL, 1.05 mmol), K2CO3 (241 mg, 1.74 mmol) and n-Bu4NI (6.4 mg, 17 μmol) in acetone (4.0 mL) were heated at reflux overnight. Purification by PTLC using AcOEt:hexane=6:4 (v/v) as eluent gave 28k as a clear oil (38 mg, 51%).
Reaction SMILES: [CH3:1][C:2]([S:5]([C:8]1[CH:13]=[CH:12][C:11]([N:14]2[NH:23][C:22](=O)[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15]2=[O:25])=[CH:10][CH:9]=1)(=[O:7])=[O:6])([CH3:4])[CH3:3].P(Br)(Br)([Br:28])=O>O>[Br:28][C:22]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15](=[O:25])[N:14]([C:11]2[CH:12]=[CH:13][C:8]([S:5]([C:2]([CH3:4])([CH3:3])[CH3:1])(=[O:7])=[O:6])=[CH:9][CH:10]=2)[N:23]=1
Reactant: CC(C)(C)S(=O)(=O)c1ccc(-n2[nH]c(=O)c3ccccc3c2=O)cc1
Reactant: O=P(Br)(Br)Br
Solvent: O
Product: CC(C)(C)S(=O)(=O)c1ccc(-n2nc(Br)c3ccccc3c2=O)cc1
Temperature: 25 °C
Yield: 25.4 %

Procedure:
2-[4-(2-methyl-propane-2-sulfonyl)-phenyl]-2,3-dihydro-phthalazine-1,4-dione (0.20 g, 0.56 mmol) and phosphorus oxybromide (0.48 g, 1.7 mmol) were stirred at 150° C. for 1 h. H2O (50 ml) was added after cooling to RT. Extraction with DCM, drying of the combined organic phases over Na2SO4, evaporation of the solvent and purification of the raw product by preparative HPLC yielded the desired compound (0.06 g, 18%). 1H-NMR: (400 MHz, D6-DMSO) 8.41 (1H, d), 8.07 (1H, d), 8.03-8.10 (4H, m), 7.80 (2H, d), 1.30 (9H, s); MS (API+)=423.0 (M+H)+.
Reaction SMILES: [C:1]([O:4][CH2:5][C@@H:6]1[C@:14]2([CH3:15])[C@@:9]([OH:24])([CH2:10][C@@H:11]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][OH:23])[CH:17]=3)[CH2:12][CH2:13]2)[CH2:8][CH2:7]1)(=[O:3])[CH3:2].[C:25]([Si:29]([CH3:32])([CH3:31])Cl)([CH3:28])([CH3:27])[CH3:26]>>[C:1]([O:4][CH2:5][C@@H:6]1[C@:14]2([CH3:15])[C@@:9]([OH:24])([CH2:10][C@@H:11]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][O:23][Si:29]([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:32])[CH3:31])[CH:17]=3)[CH2:12][CH2:13]2)[CH2:8][CH2:7]1)(=[O:3])[CH3:2]
Reactant: CC(=O)OC[C@H]1CC[C@]2(O)C[C@@H](c3cccc(CO)c3)CC[C@]12C
Reactant: CC(C)(C)[Si](C)(C)Cl
Product: CC(=O)OC[C@H]1CC[C@]2(O)C[C@@H](c3cccc(CO[Si](C)(C)C(C)(C)C)c3)CC[C@]12C

Procedure:
Starting from 3.05 g of (1S,3aS,5S,7aR)-1-acetoxymethyl-5-(3-hydroxymethylphenyl)-7a-methylperhydroinden-3a-ol, by reaction with tert-butyldimethylchlorosilane using the procedure described by Kendall P. M. et al., (J. Org. Chem. 1979, 44, 1421), 3.88 g of (1S,3aS,5S,7aR)-1-acetoxymethyl-5-(3-tert-butyldimethylsilyloxymethylphenyl)-7a-methylperhydroinden-3a-ol were obtained as a white foam. The crude product was dissolved in 30 ml of methanol and 9 ml of 4N NaOH were added. After stirring at room temperature for 8 hrs, the reaction mixture was neutralised with 3N HCl, concentrated in vacuo and extracted with ethyl acetate. The organic layer was dried over sodium sulfate and evaporated to dryness under reduced pressure to give 3.17 g of (1S,3aS,5S,7aR)-1-hydroxymethyl-5-(3-tert-butyldimethylsilyloxymethylphenyl)-7a-methylperhydroinden-3a-ol as a white solid.