Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([Cl:12])[C:3]=1[C:13]1[C:17]([N+:18]([O-])=O)=[C:16]([S:21][CH3:22])[N:15]([CH3:23])[N:14]=1.[H][H]>C(O)C.[C].[Pd]>[NH2:18][C:17]1[C:13]([C:3]2[C:4]([Cl:12])=[CH:5][C:6]([C:8]([F:10])([F:11])[F:9])=[CH:7][C:2]=2[Cl:1])=[N:14][N:15]([CH3:23])[C:16]=1[S:21][CH3:22]
Reactant: CSc1c([N+](=O)[O-])c(-c2c(Cl)cc(C(F)(F)F)cc2Cl)nn1C
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CSc1c(N)c(-c2c(Cl)cc(C(F)(F)F)cc2Cl)nn1C
Reaction time: 1 h
Yield: 433.7 %

Procedure:
A suspension of 0.15 g of 3-(2,6-dichloro-4-trifluoromethylphenyl)-1-methyl-5-methylsulfenyl-4-nitropyrazole (compound 13) and 0.1 g of 10% palladium carbon in ethanol was stirred for 1 hour while introducing hydrogen gas into the mixture at room temperature at atmospheric pressure. The reaction mixture was filtered through Celite, the filtrate was concentrated under reduced pressure, and the resulting residue was purified by column chromatography on silica gel (eluent: ether/hexane=1/4) to obtain 0.6 g of the desired compound in the form of a consistent liquid (yield 67.3%).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:20])[CH:5]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[N:6]1[CH:10]=[C:9]([N+:11]([O-])=O)[N:8]=[CH:7]1)[CH3:2].[C:21]([NH:24][C:25]1[CH:35]=[CH:34][CH:33]=[C:27]2[C:28]([O:30][C:31](=[O:32])[C:26]=12)=[O:29])(=[O:23])[CH3:22]>C(OCC)(=O)C>[CH2:1]([O:3][C:4](=[O:20])[CH:5]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[N:6]1[CH:10]=[C:9]([NH:11][C:28](=[O:29])[C:27]2[CH:33]=[CH:34][CH:35]=[C:25]([NH:24][C:21](=[O:23])[CH3:22])[C:26]=2[C:31]([OH:32])=[O:30])[N:8]=[CH:7]1)[CH3:2]
Reactant: CC(=O)Nc1cccc2c1C(=O)OC2=O
Reactant: CCCCCCC(C(=O)OCC)n1cnc([N+](=O)[O-])c1
Solvent: CCOC(C)=O
Product: CCCCCCC(C(=O)OCC)n1cnc(NC(=O)c2cccc(NC(C)=O)c2C(=O)O)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 21.7 %

Procedure:
Following the procedure of Example 2, 1.54 g of 4-nitro-α-hexyl-1H-imidazole-1-acetic acid ethyl ester were hydrogenated to the corresponding amine and allowed to react with 1.12 g of 3-acetamidophthalic anhydride in ethyl acetate. After stirring at room temperature, the solution was concentrated in vacuo and a small amount ethyl acetate added. After sitting overnight, the resulting solid was collected by filtration. Crystallization from hot ethyl acetate/methanol/hexanes provided 0.54 g of the desired intermediate, m.p. 144°-145° C. NMR.
Reaction SMILES: C(O)(C(F)(F)F)=O.C(OC([NH:15][C@@H:16]([CH2:61][OH:62])[C:17]([NH:19][CH2:20][CH2:21][O:22][C:23]1[CH:24]=[C:25]([CH:58]=[CH:59][CH:60]=1)[CH2:26][O:27][CH2:28][C@H:29]([NH:34][C:35](=[O:57])[CH2:36][N:37]1[CH:41]=[C:40]([CH2:42][O:43][C:44]2[CH:56]=[CH:55][C:47]3[N:48]=[C:49]([S:51](=[O:54])(=[O:53])[NH2:52])[S:50][C:46]=3[CH:45]=2)[N:39]=[N:38]1)[C:30]([O:32]C)=[O:31])=[O:18])=O)(C)(C)C>C(Cl)Cl>[NH2:15][C@@H:16]([CH2:61][OH:62])[C:17]([NH:19][CH2:20][CH2:21][O:22][C:23]1[CH:24]=[C:25]([CH:58]=[CH:59][CH:60]=1)[CH2:26][O:27][CH2:28][C@H:29]([NH:34][C:35](=[O:57])[CH2:36][N:37]1[CH:41]=[C:40]([CH2:42][O:43][C:44]2[CH:56]=[CH:55][C:47]3[N:48]=[C:49]([S:51](=[O:53])(=[O:54])[NH2:52])[S:50][C:46]=3[CH:45]=2)[N:39]=[N:38]1)[C:30]([OH:32])=[O:31])=[O:18]
Reactant: COC(=O)[C@H](COCc1cccc(OCCNC(=O)[C@H](CO)NC(=O)OC(C)(C)C)c1)NC(=O)Cn1cc(COc2ccc3nc(S(N)(=O)=O)sc3c2)nn1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: N[C@@H](CO)C(=O)NCCOc1cccc(COC[C@H](NC(=O)Cn2cc(COc3ccc4nc(S(N)(=O)=O)sc4c3)nn2)C(=O)O)c1
Reaction time: 0.5 h

Procedure:
To a 10 mL vial with magnetic stir bar was added DCM (0.5 mL) and TFA (0.5 mL). To this, compound 70 was added and let to react for 30 min. After the completion of the reaction, solvents were removed in vacuo, THF was added (0.2 mL) followed by aq. LiOH (0.4 mL) and the reaction stirred for 30 min. After completion of the reaction, THF was removed and the crude residue was purified by HPLC to afford VM3163 (33%) as a colorless solid. LCMS for C27H32N8O10S2, calc'd: 692.17, found: 693.0 (M+H).
Reaction SMILES: [CH3:1][C@H:2]1[C@@H:19]([CH3:20])[N:6]2[C:7]3[CH:8]=[C:9]([C:14]([O:16]CC)=[O:15])[CH:10]=[CH:11][C:12]=3[CH:13]=[C:5]2[C:4](=[O:21])[NH:3]1.[OH-].[Na+].Cl>C(O)C>[CH3:1][C@H:2]1[C@@H:19]([CH3:20])[N:6]2[C:7]3[CH:8]=[C:9]([C:14]([OH:16])=[O:15])[CH:10]=[CH:11][C:12]=3[CH:13]=[C:5]2[C:4](=[O:21])[NH:3]1
Reactant: CCOC(=O)c1ccc2cc3n(c2c1)[C@H](C)[C@H](C)NC3=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: C[C@@H]1NC(=O)c2cc3ccc(C(=O)O)cc3n2[C@@H]1C
Temperature: 80 °C
Yield: 98.1 %

Procedure:
Ethyl (3S,4R)-3,4-dimethyl-1-oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indole-7-carboxylate (870 mg, 3.0 mmol) is suspended in ethanol (25 mL) and 1M NaOH solution (7.6 mL, 7.6 mmol) is added. The reaction mixture is heated at 80° C. for 1 h and then cooled to room temperature. The mixture is acidified with 1M HCl solution and ethanol is removed. The resulting solid is filtered, rinsed with water and dried to afford the title compound (760 mg, 97%).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][Cl:6].[OH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:23]([CH3:24])[C:22](=[O:25])[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([O:26][CH3:27])[CH:20]=3)[N:15]=2)=[CH:10][CH:9]=1>CS(C)=O>[Cl:6][CH2:5][CH2:4][CH2:3][CH2:2][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[N:23]([CH3:24])[C:22](=[O:25])[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([O:26][CH3:27])[CH:20]=3)[N:15]=2)=[CH:10][CH:9]=1
Reactant: ClCCCCBr
Reactant: COc1ccc2nc(-c3ccc(O)cc3)n(C)c(=O)c2c1
Solvent: CS(C)=O
Product: COc1ccc2nc(-c3ccc(OCCCCCl)cc3)n(C)c(=O)c2c1
Temperature: 25 °C

Procedure:
4 gm (0.014 mol) of the product in (b) were dissolved in 30 ml of dimethylsulfoxide, and the solution was mixed, while stirring, with 1.75 gm (0.014 mol+10%) of potassium tert. butylate. Subsequently, 4 ml of 1-bromo-4-chlorobutane were added, and the reaction mixture was stirred at room temperature until the reaction was complete. The reaction mixture was poured into ice water, and the crystalline precipitate thus formed was suction-filtered off, washed well with water and dried.
Reaction SMILES: [I-].[K+].[CH2:3]([O:5][C:6]([CH:8]1[CH2:17][N:16]([CH2:18][CH3:19])[C:15]2[N:14]=[C:13]3[CH:20]=[C:21]([F:25])[C:22]([F:24])=[CH:23][C:12]3=[CH:11][C:10]=2[C:9]1=[O:26])=[O:7])[CH3:4].OO.S([O-])([O-])(=O)=S.[Na+].[Na+]>O.C(O)C>[CH2:3]([O:5][C:6]([C:8]1[C:9](=[O:26])[C:10]2[CH:11]=[C:12]3[CH:23]=[C:22]([F:24])[C:21]([F:25])=[CH:20][C:13]3=[N:14][C:15]=2[N:16]([CH2:18][CH3:19])[CH:17]=1)=[O:7])[CH3:4]
Reactant: CCOC(=O)C1CN(CC)c2nc3cc(F)c(F)cc3cc2C1=O
Agent: O=S([O-])([O-])=S
Agent: OO
Agent: [I-]
Solvent: CCO
Solvent: O
Product: CCOC(=O)c1cn(CC)c2nc3cc(F)c(F)cc3cc2c1=O
Temperature: 77 °C
Yield: 87.5 %

Procedure:
A solution of 1.7 g of potassium iodide in 10 cm3 of water is added with stirring at approximately 20° C. to a suspension of 33 g of 3-ethoxycarbonyl-7,8-difluoro-1-ethyl-4-oxo-1,2,3,4-tetrahydrobenzo[b][1,8]naphthyridine in 1,000 cm3 of ethanol. The suspension is heated to 77° C., and 12.7 cm3 of 33% by weight hydrogen peroxide are introduced in the course of 30 minutes at this temperature. The reaction mixture is kept refluxing for a further 30 minutes and is then cooled to approximately 20° C. A solution of 6 g of sodium thiosulphate in 20 cm3 of water is introduced in the course of 5 minutes at this temperature. The precipitate obtained is drained at approximately 20° C. and washed with twice 150 cm3 of water. The wet product obtained is dried under reduced pressure (20 kPa) at approximately 50° C. 28.7 g of 3-ethoxycarbonyl-7,8-difluoro-1-ethyl-4-oxo-1,4-dihydrobenzo[b][1,8]-naphthyridine are isolated in the form of a light yellow solid, melting point 270° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[CH:9]=[C:8]([C:15]([OH:17])=O)[CH2:7][CH2:6]2.O=S(Cl)[Cl:20]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[CH:9]=[C:8]([C:15]([Cl:20])=[O:17])[CH2:7][CH2:6]2
Reactant: O=S(Cl)Cl
Reactant: COc1cc2c(cc1OC)CCC(C(=O)O)=C2
Solvent: Cc1ccccc1
Product: COc1cc2c(cc1OC)CCC(C(=O)Cl)=C2
Temperature: 50 °C

Procedure:
A mixture of 6,7-dimethoxy-3,4-dihydronaphthalene-2-carboxylic acid (476 mg, 2 mmol) and SOCl2 (1.5 mL, 20 mmol) in toluene (20 mL) was heated at 50° C. for 1 hour. The solvent was then removed under reduced pressure to give 6,7-dimethoxy-3,4-dihydronaphthalene-2-carbonyl chloride which was used directly in the next step without further purification. To a stirred solution of methyl 2-aminobenzoate (332 mg, 2.2 mmol) and Et3N (0.8 mL, 6 mmol) in anhydrous DCM (20 mL) was added 6,7-dimethoxy-3,4-dihydronaphthalene-2-carbonyl chloride in anhydrous DCM (2 mL) dropwise at 0° C. The resulting mixture was stirred at room temperature overnight. The reaction was quenched with water and extracted with DCM. The combined organic phase was dried over sodium sulfate, the solvent was removed under reduced pressure and the residue was purified by flash column, eluting with petroleum ether/ethyl acetate (10:1) to give methyl 2-(6,7-dimethoxy-1,2-dihydronaphthalene-3-carboxamido)benzoate (330 mg, 45%). LC-MS (ES-API); rt 9.27 min; m/z calculated for C21H21NO5 [M+Na]+ 390.1, found 390.1.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2OC)(O)[CH:11]([CH3:13])[CH3:12])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].Br.C(O)(=O)C.[OH2:28]>>[CH:1]([C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=3[O:28][C:11]2([CH3:13])[CH3:12])=[CH:6][CH:5]=1)([CH3:3])[CH3:2]
Reactant: O
Reactant: COc1ccccc1C(O)(c1ccc(C(C)C)cc1)C(C)C
Agent: Br
Solvent: CC(=O)O
Product: CC(C)c1ccc(C2c3ccccc3OC2(C)C)cc1
Yield: 89 %

Procedure:
A mixture of 1-(4-isopropylphenyl)-1-(2-methoxyphenyl)-2-methylpropan-1-ol obtained in Reference Example 82 (3.4 g, 11.4 mmol), 48% hydrobromic acid (50 mL) and acetic acid (10 mL) was heated under reflux under argon atmosphere for 16 hours. After cooling, water was added to the reaction solution, which was extracted with ethyl acetate, and the combined organic layer was washed with water, dried over magnesium sulfate, filtered and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=20:1) to obtain 2.71 g (yield 89%) of the title compound. Oily matter.
Reaction SMILES: [CH3:1]C1C=CC2C(=O)C3C=CC=CC=3C=CC=2C=1.BrN1C(=O)CCC1=O.[Br:26][CH2:27][C:28]1[CH:43]=[CH:42][C:31]2[C:32](=[O:41])[C:33]3[CH:40]=[CH:39][CH:38]=[CH:37][C:34]=3[CH:35]=[CH:36][C:30]=2[CH:29]=1.C(C1C=CC2C(=O)C3C=CC=CC=3C=CC=2C=1)C>C(Cl)(Cl)(Cl)Cl>[Br:26][CH:27]([C:28]1[CH:43]=[CH:42][C:31]2[C:32](=[O:41])[C:33]3[CH:40]=[CH:39][CH:38]=[CH:37][C:34]=3[CH:35]=[CH:36][C:30]=2[CH:29]=1)[CH3:1]
Reactant: Cc1ccc2c(=O)c3ccccc3ccc2c1
Reactant: O=c1c2ccccc2ccc2cc(CBr)ccc12
Agent: CCc1ccc2c(=O)c3ccccc3ccc2c1
Agent: O=C1CCC(=O)N1Br
Solvent: ClC(Cl)(Cl)Cl
Product: CC(Br)c1ccc2c(=O)c3ccccc3ccc2c1
Yield: 80 %

Procedure:
39.7 Gm. of 2-methyl-5H-dibenzo[a,d]cyclohepten-5-one is refluxed in 1200 ml. of carbon tetrachloride with 35.2 gm. of N-bromosuccinimide for 14 hours, irradiating with a 100 watt incandescent lamp. The solution is cooled, filtered and evaporated. The residue is recrystallized from methylene chloride/hexane to afford 27.3 gm., 51%, of 2-bromomethyl-5H-dibenzo[a,d]cyclohepten-5-one, m.p. 128°-132° C. Use of 2-ethyl-5H-dibenzo[a,d]cyclohepten-5-one gives 80% of 2-(α-bromoethyl)-5H-dibenzo[a,d]cyclohepten-5-one, m.p. 93°-95° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][CH3:12])(=[O:10])=[O:9])=[CH:4][C:3]=1[N+:13]([O-])=O.[NH4+].[Cl-]>CCO.O.[Fe]>[NH2:13][C:3]1[CH:4]=[C:5]([S:8]([NH:11][CH3:12])(=[O:9])=[O:10])[CH:6]=[CH:7][C:2]=1[Cl:1]
Reactant: CNS(=O)(=O)c1ccc(Cl)c([N+](=O)[O-])c1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: CNS(=O)(=O)c1ccc(Cl)c(N)c1
Temperature: 90 °C
Yield: 100.3 %

Procedure:
A solution of 4-chloro-N-methyl-3-nitrobenzenesulfonamide (6.35 g, 25.3 mmol) in EtOH (150 mL) and water (50.0 mL) was treated with iron (14.15 g, 253 mmol) and NH4Cl (13.55 g, 253 mmol) and heated at 90° C. for 4 hours before being cooled and filtered through celite. The filter cake was washed with EtOAc and the combined filtrate was filtered again to remove precipitated NH4Cl before being concentrated. The resulting crude material was partitioned between 350 ml EtOAc and 50 ml saturated aqueous NaHCO3. The organic layer was washed with brine, dried over MgSO4, concentrated and subjected to flash column chromatography (330 g silica gel, 0-15% EtOAc/DCM) to afford 3-amino-4-chloro-N-methylbenzenesulfonamide (5.60 g, 100%) as a light yellow crystalline solid. 1H NMR (400 MHz, MeOD) δ ppm 7.39 (d, J=8.28 Hz, 1 H), 7.27 (d, J=2.26 Hz, 1 H), 7.03 (dd, J=8.28, 2.26 Hz, 1 H), 2.54 (s, 3 H). MS 221.0 (M+H+).
Reaction SMILES: [CH3:1][N:2]([CH3:7])[S:3](Cl)(=[O:5])=[O:4].[CH3:8][O:9][C:10]1[CH:11]=[C:12]([CH3:31])[CH:13]=[C:14]2[C:18]=1[CH:17]([NH:19][C:20]1[CH:29]=[CH:28][C:27]3[C:22](=[CH:23][CH:24]=[C:25]([NH2:30])[CH:26]=3)[N:21]=1)[CH2:16][CH2:15]2>>[CH3:8][O:9][C:10]1[CH:11]=[C:12]([CH3:31])[CH:13]=[C:14]2[C:18]=1[CH:17]([NH:19][C:20]1[CH:29]=[CH:28][C:27]3[C:22](=[CH:23][CH:24]=[C:25]([NH:30][S:3]([N:2]([CH3:7])[CH3:1])(=[O:5])=[O:4])[CH:26]=3)[N:21]=1)[CH2:16][CH2:15]2
Reactant: CN(C)S(=O)(=O)Cl
Reactant: COc1cc(C)cc2c1C(Nc1ccc3cc(N)ccc3n1)CC2
Product: COc1cc(C)cc2c1C(Nc1ccc3cc(NS(=O)(=O)N(C)C)ccc3n1)CC2

Procedure:
The title compound was prepared in accordance with the general method described in example 66 from dimethylsulfamoylchloride and rac-N2-(7-methoxy-5-methyl-indan-1-yl)-quinoline-2,6-diamine; MS: m/e=427.6 (M+H+).
Reaction SMILES: IC1C=CC=CC=1S([O-])(=O)=O.[Na+].OOS([O-])=O.[K+].S([O-])([O-])(=O)=O.[Na+].[Na+].[CH2:26]([OH:44])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]/[CH:34]=[CH:35]\[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43]>[N+](C)([O-])=O>[CH:26](=[O:44])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]/[CH:34]=[CH:35]\[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43]
Reactant: CCCCCCCC/C=C\CCCCCCCCO
Agent: O=S(=O)([O-])[O-]
Agent: O=S(=O)([O-])c1ccccc1I
Agent: O=S([O-])OO
Solvent: C[N+](=O)[O-]
Product: CCCCCCCC/C=C\CCCCCCCC=O
Temperature: 70 °C
Reaction time: 2 h
Yield: 90 %

Procedure:
6.1 mg (0.02 mmol) of Sodium 2-iodobenzenesulfonate prepared by Preparation Example 4, 0.37 g (0.6 mmol) of powdered Oxone (registered trademark), 0.5 g (3.5 mmol) of anhydrous sodium sulfate, and 268 mg (1 mmol) of (Z)-octadeca-9-en-1-ol were added to 5 ml of nitromethane, and the mixture was heated at 70° C. while being stirred under a nitrogen for two hours. The later treatment was carried out in the same way as in Example 1, and then (Z)-olealdehyde was obtained. The yield of the obtained (Z)-olealdehyde was determined and the result is shown in Table 2. (Yield 90%)
Reaction SMILES: [O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:7]=[C:8](/[CH:15]=[CH:16]/[C:17]([O:19][CH3:20])=[O:18])[S:9][C:10]=1[Si](C)(C)C.O.O1CCCC1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl-].[NH4+]>O1CCCC1>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:7]=[C:8](/[CH:15]=[CH:16]/[C:17]([O:19][CH3:20])=[O:18])[S:9][CH:10]=1
Reactant: COC(=O)/C=C/c1cc(C2OCCO2)c([Si](C)(C)C)s1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Agent: [F-]
Solvent: O
Solvent: C1CCOC1
Product: COC(=O)/C=C/c1cc(C2OCCO2)cs1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 99.7 %

Procedure:
To a solution of methyl (2E)-3-[4-(1,3-dioxolan-2-yl)-5-(trimethylsilyl)thiophen-2-yl]acrylate (4.000 g, 12.80 mmol) in tetrahydrofuran (20 ml) was added water (0.2 ml), and the mixture was cooled to 0° C. Tetrabutylammoniumfluoride tetrahydrofuran solution (1M, 13.4 ml, 13.4 mmol) was added, and the mixture was stirred at 0° C. for 5 min and at room temperature for 10 min. The mixture was cooled to 0° C., saturated aqueous ammonium chloride solution (40 ml) was added, and the mixture was extracted 3 times with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (FUJI SILYSIA CHEMICAL LTD. BW-300SP 200 g, ethyl acetate:hexane=1:3) to give methyl (2E)-3-[4-(1,3-dioxolan-2-yl)thiophen-2-yl]acrylate (3.065 g, 12.76 mmol, 99.7%) as a colorless oil.
Reaction SMILES: [Br:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[CH:4][CH:3]=1.S(Cl)([Cl:12])=O>CN(C)C=O.C(Cl)(Cl)Cl>[Br:1][C:2]1[S:6][C:5]([C:7]([Cl:12])=[O:9])=[CH:4][CH:3]=1
Reactant: O=C(O)c1ccc(Br)s1
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Solvent: ClC(Cl)Cl
Product: O=C(Cl)c1ccc(Br)s1
Yield: 99.1 %

Procedure:
A mixture of 5-bromothiophene-2-carboxylic acid (300 mg, 1.45 mmol), thionyl chloride (423 μL, 5.80 mmol), and N,N-dimethylformamide (1 drop) was dissolved in chloroform (3 mL), and refluxed for 1 hour. After cooling down, the reaction mixture was concentrated under reduced pressure to give the titled reference compound (324 mg) as a pale yellow solid. (Yield 99%)
Reaction SMILES: F[C:2](F)(F)[C:3]([O:5][C:6](=[O:11])[C:7]([F:10])([F:9])[F:8])=O.N1C=CC=CC=1.O[C@@H]1[CH2:40][CH2:39][C@@:38]2([CH3:41])[C@@H:23]([CH2:24][CH2:25][C@@H:26]3[C@@H:37]2[C:36](=[O:42])[CH2:35][C@@:34]2([CH3:43])[C@H:27]3[CH2:28][CH2:29][C@@H:30]2[C:31](=[O:33])[CH3:32])C1>C(Cl)Cl>[F:8][C:7]([F:10])([F:9])[C:6]([O:5][C@@H:3]1[CH2:40][CH2:39][C@@:38]2([CH3:41])[C@@H:23]([CH2:24][CH2:25][C@@H:26]3[C@@H:37]2[C:36](=[O:42])[CH2:35][C@@:34]2([CH3:43])[C@H:27]3[CH2:28][CH2:29][C@@H:30]2[C:31](=[O:33])[CH3:32])[CH2:2]1)=[O:11]
Reactant: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Reactant: CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](O)CC[C@]4(C)[C@H]3C(=O)C[C@]12C
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@H](OC(=O)C(F)(F)F)CC[C@]4(C)[C@H]3C(=O)C[C@]12C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of trifluoroacetic anhydride (0.34 ml.) and pyridine (0.24 ml.) in methylene dichloride (10 ml.) was added to a cooled (-80°) and stirred solution of 3α-hydroxy-5α-pregnane-11,20-dione (0.50 g.) in methylene dichloride (20 ml.) and the mixture was allowed to warm up to room temperature. After 11/2 hours more trifluoroacetic anhydride (0.34 ml.) was added and the reaction was complete after 1/2 hour more. The solution was washed successively with water, sodium bicarbonate solution and water. The dried and concentrated solution afforded a crystalline residue that was triturated with petroleum to give the title compound as needles (0.44 g.) m.p. 107°-108°, [α]D + 96°.
Reaction SMILES: [CH3:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([CH3:10])[C:3]=1[CH2:4]O.S(Cl)([Cl:13])=O>>[CH3:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([CH3:10])[C:3]=1[CH2:4][Cl:13]
Reactant: Cc1cccc(C)c1CO
Reactant: O=S(Cl)Cl
Product: Cc1cccc(C)c1CCl
Reaction time: 6 h

Procedure:
To a stirred solution of 2,6-Dimethylbenzyl alcohol (9.94 g, 73 mmol) was added thionyl chloride (81.55 g, 685 mmol) at room temperature. The reaction mixture was stirred for 6 hours, concentrated under reduced pressure and used without further purification.
Reaction SMILES: [CH3:1][Si:2]([CH3:12])([CH3:11])[C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH2:6][OH:7].C1C=CC(N=NC2C=CC(N)=NC=2N)=CC=1.Cl.[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.C(O)(=O)C>ClCCl>[CH3:1][Si:2]([CH3:12])([CH3:11])[C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH:6]=[O:7]
Reactant: C[Si](C)(C)c1cccc(CO)c1
Agent: O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]
Agent: Cl
Agent: Nc1ccc(N=Nc2ccccc2)c(N)n1
Solvent: CC(=O)O
Solvent: ClCCl
Product: C[Si](C)(C)c1cccc(C=O)c1
Reaction time: 0.33 h

Procedure:
To a mixture of 3-trimethylsilylbenzylalcohol (3.60 g, 20 mmol) and pyridium dichromate (11.29 g, 30 mmol) in dichloromethane (60 ml) at 0° C. was added 3 Å molecular sieve powder (16 g) and anhydrous acetic acid (2 ml). Then the reaction was allowed to react 30 min at room temperature, stirred 20 min with celite (10 g), filtered and evaporated under reduced pressure. The residue was treated with diethyl ether (50 ml), filtered through MgSO4 and concentrated. 3-trimethylsilylbenzaldehyde was purified by distillation.
Reaction SMILES: [CH2:1]([NH2:5])[CH:2]([CH3:4])[CH3:3].[CH3:6][N:7]([O:20][CH3:21])[C:8](=[O:19])[C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[C:11](F)[CH:10]=1>C(#N)C>[CH3:6][N:7]([O:20][CH3:21])[C:8](=[O:19])[C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[C:11]([NH:5][CH2:1][CH:2]([CH3:4])[CH3:3])[CH:10]=1
Reactant: CC(C)CN
Reactant: CON(C)C(=O)c1ccc([N+](=O)[O-])c(F)c1
Solvent: CC#N
Product: CON(C)C(=O)c1ccc([N+](=O)[O-])c(NCC(C)C)c1
Temperature: 25 °C
Yield: 90 %

Procedure:
Add isobutylamine (8.7 mL) dropwise to a solution of N-[methyl]-N-[methoxy]-3-fluoro-4-nitrobenzamide (2 g, 8.77 mmol) in 80 mL dry acetonitrile at 0° C. Stir the resulting orange solution at room temperature over night. Concentrate under reduced pressure to provide the desired compound (90%).
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[S:11](Cl)(=[O:13])=[O:12].[NH2:15][C@@H:16]([C:24]([OH:26])=[O:25])[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CCOCC.[OH-].[Na+]>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[S:11]([NH:15][C@@H:16]([C:24]([OH:26])=[O:25])[CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)(=[O:13])=[O:12]
Reactant: O=S(=O)(Cl)c1ccc2ccccc2c1
Reactant: N[C@H](Cc1ccccc1)C(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Product: O=C(O)[C@@H](Cc1ccccc1)NS(=O)(=O)c1ccc2ccccc2c1
Reaction time: 15 h
Yield: 91.7 %

Procedure:
20 g of 2-naphthylsulphonyl chloride in 150 ml of ether are added to a solution of 7.3 g of (R)-phenylalanine in 120 ml of 1N sodium hydroxide solution. The reaction mixture is stirred for 15 hours and decanted. The aqueous phase is separated, washed with ether, acidified to pH 3 with HCl and extracted with ethyl acetate. The organic phase is dried and evaporated. The separated crystals are suspended in ether and filtered off. There are obtained 14.4 g of N-(2-naphthylsulfonyl)-3-phenyl-D-alanine, m.p. 146° C.
Reaction SMILES: N1C(C)=CC=CC=1C.[CH2:9]([O:16][C:17]1[CH:18]=[CH:19][C:20]([C@@H:28]([OH:31])[CH2:29][Br:30])=[C:21]2[C:26]=1[NH:25][C:24](=[O:27])[CH:23]=[CH:22]2)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.FC(F)(F)S(O[Si:38]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39])(=O)=O>C(Cl)Cl>[CH2:9]([O:16][C:17]1[CH:18]=[CH:19][C:20]([C@@H:28]([O:31][Si:38]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39])[CH2:29][Br:30])=[C:21]2[C:26]=1[NH:25][C:24](=[O:27])[CH:23]=[CH:22]2)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F
Reactant: O=c1ccc2c([C@@H](O)CBr)ccc(OCc3ccccc3)c2[nH]1
Solvent: Cc1cccc(C)n1
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)O[C@@H](CBr)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Reaction time: 0.08 h
Yield: 85.7 %

Procedure:
2,6-Lutidine (6.9 mL, 59.5 mmol) was added to a solution of (R)-8-(benzyloxy)-5-(2-bromo-1-hydroxyethyl)quinolin-2(1H)-one (10.1 g, 27.0 mmol) in DCM (100 mL) at 0° C. The reaction mixture was stirred for 5 minutes then tert-butyldimethylsilyl trifluoromethanesulfonate (13.0 mL, 56.8 mmol) was added dropwise over 15 minutes. The mixture was stirred at 0° C. for 30 minutes, followed by RT overnight. After this time the reaction was quenched with saturated aqueous sodium bicarbonate solution and extracted with DCM (×3). The combined organic extracts were dried (magnesium sulfate), filtered and concentrated under reduced pressure. Iso-hexane (500 mL) was added to the crude material and the resulting solid collected by filtration. The solid was recrystallised from ethyl acetate and petroleum ether (40:60) to afford the title compound (11.3 g, 85%).