Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][CH2:10][CH2:11][C:12](=[O:14])[CH3:13])=[CH:4][N:3]=1.[OH-].[Na+].O>CO>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:9][CH2:10][CH2:11][C:12](=[O:14])[CH:13]=2)=[CH:4][N:3]=1
Reactant: CC(=O)CCCC(=O)c1ccc(C)nc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: Cc1ccc(C2=CC(=O)CCC2)cn1
Temperature: 25 °C
Reaction time: 1 h
Yield: 82 %

Procedure:
A 72.2 g. portion of 1-(2-methyl-5-pyridinyl)hexan-1,5-dione was dissolved in 200 ml. of methanol and added to a solution containing 50 g. of sodium hydroxide in 500 ml. of water plus 100 ml. of methanol. The reaction mixture was stirred for one hour at room temperature and the methanol was then distilled off in vacuo at a low temperature. The remaining aqueous mixture was extracted four times with ether; the ether extracts were combined, dried over anhydrous sodium sulfate and filtered; and, the dried ether solution was stripped in vacuo to remove the ether and to yield 54 g. (82% yield) of 3-(2-methyl-5-pyridinyl)-2-cyclohexen-1-one. This 54 g. portion of 2-(2-methyl-5-pyridinyl)-2-cyclohexen-1-one was converted, as in Example C-3, to 36.0 g. (62% yield) of the corresponding oxime derivative, m.p. 171°-173° C. The 10 g. portion of this oxime was converted, as in Example D-3, to 6.4 g. of 5-(3-aminophenyl)-2-methylpyridine, m.p. 115°-116° C., using 8.5 ml. of acetic anhydride and 70 ml. of acetic acid and gaseous hydrogen chloride for one hour while heating the reaction mixture at 80°-90° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[CH2:5][N:6]1[C:14](=[O:15])[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:16]([OH:18])=O)[CH:12]=2)[C:7]1=[O:19].[O:23]1[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][NH2:31])[CH2:25][CH2:24]1>>[Cl-:1].[Cl:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][CH:22]=1)[CH2:5][N:6]1[C:14](=[O:15])[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:16]([NH:31][CH2:30][CH2:29][NH+:26]3[CH2:27][CH2:28][O:23][CH2:24][CH2:25]3)=[O:18])[CH:12]=2)[C:7]1=[O:19]
Reactant: O=C(O)c1ccc2c(c1)C(=O)N(Cc1cccc(Cl)c1)C2=O
Reactant: NCCN1CCOCC1
Product: O=C(NCC[NH+]1CCOCC1)c1ccc2c(c1)C(=O)N(Cc1cccc(Cl)c1)C2=O
Product: [Cl-]

Procedure:
2-(3-chloro-benzyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-carboxylic acid (100 mg, 0.316 mmol) and 2-morpholinoethane amine (103 μL, 0.792 mmol) were reacted with each other. Target compound in the amount of 59 mg (40%) was obtained by following the procedure described in Example 1.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[S:10])=[CH:4][CH:3]=1.Cl.[O-:12][Mn](=O)(=O)=O.[K+].[CH3:18][N:19]=[C:20]=[O:21]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:9](=[O:12])[S:10][N:19]([CH3:18])[C:20]2=[O:21])=[CH:4][CH:3]=1
Reactant: CN=C=O
Reactant: O=[Mn](=O)(=O)[O-]
Reactant: S=C=Nc1ccc(Cl)cc1
Agent: Cl
Agent: [K+]
Product: Cn1sc(=O)n(-c2ccc(Cl)cc2)c1=O

Procedure:
Reagents: 4-Chlorophenyl isothiocyanate (1.1 g, 6.5 mmol), 35% HCl (3.1 ml), KMnO4 (0.5 g), methyl isocyanate (0.38 ml, 6.5 mmol).
Reaction SMILES: [Cl:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][CH:5]=[CH:4][N:3]=1.[CH:11]([Mg]Br)=[CH2:12]>C1COCC1>[ClH:1].[NH:8]1[C:7]2=[CH:2][N:3]=[CH:4][CH:5]=[C:6]2[CH:12]=[CH:11]1
Reactant: O=[N+]([O-])c1cccnc1Cl
Reactant: C=C[Mg]Br
Solvent: C1CCOC1
Product: Cl
Product: c1cc2cc[nH]c2cn1
Temperature: 25 °C
Yield: 12.8 %

Procedure:
A solution of 2-chloro-3-nitropyridine (4.76 g, 30.0 mmol) in THF (50 ml) was stirred at −70° C. and therein was dropped in a period of 40 minutes vinyl magnesium bromide (1.0 M in THF, 80.0 ml, 80.0 mmol). The mixture was warmed to room temperature and stirred over night. The reaction mixture was quenched with aqueous ammonium solution, made alkaline with aqueous sodium bicarbonate solution and extracted with chloroform. The organic layer was washed with water, dried over magnesium sulfate and filtered. The solvent was removed in vacuo and the residue was purified by silica gel column chromatography. Thus obtained compound was dissolved in methanol (20 ml), and thereto was added 10% palladium hydroxide-carbon (50% wet)(40 mg). The mixture was stirred at room temperature under a hydrogen atmosphere at ordinary pressure for 5 hours. The reaction mixture was filtered through Celite and the filtrate was concentrated in vacuo to give the subject compound (595 mg, 13%).
Reaction SMILES: O=[C:2]1[C:15]2[C:14]([C:16]([OH:18])=[O:17])=[CH:13][CH:12]=[CH:11][C:10]=2[C:9](=O)[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2>[Zn].[NH4+].[OH-]>[C:14]1([C:16]([OH:18])=[O:17])[C:15]2[C:10](=[CH:9][C:8]3[C:3]([CH:2]=2)=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:11]=[CH:12][CH:13]=1
Reactant: O=C(O)c1cccc2c1C(=O)c1ccccc1C2=O
Agent: [NH4+]
Agent: [OH-]
Agent: [Zn]
Product: O=C(O)c1cccc2cc3ccccc3cc12
Reaction time: 3.5 h
Yield: 81.9 %

Procedure:
To a 5 L 3-neck flask fitted with condenser, thermometer, and overhead stirrer was added 9,10-dihydro-9,10-dioxo-1-anthracenecarboxylic acid (15A, 90 g, 0.357 mol), Zn dust (Mallinckrodt, 250 g, 3.82 mol), CuSO4.5H2O (Mallinckrodt, 5 g), and 28% NH4OH (Mallinckrodt, 2500 mL). The mixture was heated slowly. A dark-red solution occured as the temperature reched 85°. After 3.5 h, the color of the solution faded to yellow. The reaction was heated an additional 1 H, cooled and the excess Zn removed by filtration. The filter cake was washed with more NH4OH solution (100 mL) and then discarded. The filtrate was carefully acidified to pH 1 with conc. HCl (added in portions over 1 h) affording a light-green precipitate, which was separated by filtration. The solid was washed with H2O (200 mL) and then recrystallized 1× from methoxyethanol/H2O (containing 1% conc. HCl), filtered and dried at 75°, to give 65 g (82%) of 1-anthracenecarboxylic acid mp 249°-250°, (C, H), (lit. mp 245°, Chemistry of Carbon Compounds IIIb, edited by E. H. Rodd, 1373 (1956), Elsevier, New York).
Reaction SMILES: [OH:1][C@H:2]([C:16]1[S:17][CH:18]=[CH:19][CH:20]=1)[C@@H:3]1[N:7]([CH3:8])[C:6](=O)[CH2:5][C@@H:4]1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:30])=CC=1.COC1C=CC(P2(=S)CP(=S)(C3C=CC(OC)=CC=3)S2)=CC=1>COCCOC>[OH:1][C@H:2]([C:16]1[S:17][CH:18]=[CH:19][CH:20]=1)[C@@H:3]1[N:7]([CH3:8])[C:6](=[S:30])[CH2:5][C@@H:4]1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: CN1C(=O)C[C@H](c2ccccc2)[C@@H]1[C@H](O)c1cccs1
Agent: COc1ccc(P2(=S)CP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: COCCOC
Product: CN1C(=S)C[C@H](c2ccccc2)[C@@H]1[C@H](O)c1cccs1
Temperature: 65 °C
Yield: 15 %

Procedure:
(±)-(4R*,5R*)-5-((1S*)-Hydroxy-2-thienylmethyl)-1-methyl-4-phenyl-pyrrolidin-2-one (Example 5, 0.30 g, 1.06 mmol) and Lawesson's Reagent ([2,4-bis(4-methoxyphenyl)-1,2-dithia-2,4-diphosphetane-2,4-disulfide; 0.22 g, 0.53 mmol) were mixed in DME (3 mL) at rt for 18 h then heated to 65° C. for another 18 h. The reaction was cooled to rt and the solvent was concentrated under reduced pressure to give a dark oil. The crude product was purified by flash chromatography (1% MeOH/99% CH2Cl2) to give (±)-(4R*,5R*)-5-((1S*)-hydroxy-2-thienylmethyl)-1-methyl-4-phenylpyrrolidin-2-thione (46 mg, 15% yield) as a yellow solid; TLC (75% EtOAc/25% hexanes) Rf 0.36; HPLC ES-MZ m/z (rel abundance) 304 ([MH]+, 100%) AT 4.8 min.
Reaction SMILES: Cl[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)=[O:4].[CH2:12]([NH:15][CH2:16][CH:17]=[CH2:18])[CH:13]=[CH2:14].O>C(#N)C>[CH2:12]([N:15]([CH2:16][CH:17]=[CH2:18])[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)=[O:4])[CH:13]=[CH2:14]
Reactant: O=C(CCl)c1ccc(F)cc1
Reactant: C=CCNCC=C
Solvent: O
Solvent: CC#N
Product: C=CCN(CC=C)CC(=O)c1ccc(F)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 118.3 %

Procedure:
2-Chloro-1-(4-fluorophenyl)ethanone (10 g, 57.4 mmol) is dissolved in acetonitrile (400 mL). The solution is cooled to 0° C. and diallylamine (15.6 mL, 126.2 mmol) is added. After 1 hour, the mixture is poured into water (500 mL) and extracted twice with ethyl acetate (400 mL). The organic extracts are combined, washed with brine (1×200 mL), dried over sodium sulfate, filtered, and concentrated to give the crude title compound (15.84 g, 118%). ES/MS (m/e): 234 (M+H).
Reaction SMILES: [Br:1][C:2]1[N:3]=[C:4]([C:9]2[O:10][C:11]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20]Br)=[CH:16][CH:15]=3)=[N:12][N:13]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.C(=O)([O-])[O-].[Na+].[Na+].[CH3:28][NH2:29]>O>[Br:1][C:2]1[N:3]=[C:4]([C:9]2[O:10][C:11]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][NH:29][CH3:28])=[CH:16][CH:15]=3)=[N:12][N:13]=2)[C:5]([NH2:8])=[N:6][CH:7]=1
Reactant: Nc1ncc(Br)nc1-c1nnc(-c2ccc(CBr)cc2)o1
Reactant: CN
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: CNCc1ccc(-c2nnc(-c3nc(Br)cnc3N)o2)cc1
Temperature: 60 °C
Yield: 85.3 %

Procedure:
5-bromo-3-[5-[4-(bromomethyl)phenyl]-1,3,4-oxadiazol-2-yl]pyrazin-2-amine (100 mg, 0.2433 mmol) and sodium carbonate (77.36 mg, 0.7299 mmol) were suspended in and treated with methanamine (182.5 μL of 2 M, 0.3650 mmol). The reaction was heated at 60° C. for 10 minutes. The remaining excess of methanamine (425.8 μL of 2 M, 0.8515 mmol) was then added and the reaction heated at 60° C. for a further 10 minutes. The reaction was cooled, diluted with water and extracted into dichloromethane. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo to yield 5-bromo-3-[5-[4-(methylaminomethyl)phenyl]-1,3,4-oxadiazol-2-yl]pyrazin-2-amine (75 mg, 0.2076 mmol, 85.34%) as a yellow solid. LC/MS m/z 362.3 [M+H]+.
Reaction SMILES: C([O:4][CH:5]([CH2:43][O:44]C(=O)C)[CH2:6][NH:7][C:8]([C:10]1[C:15]([I:16])=[C:14]([N:17]2[CH2:21][CH2:20][CH:19]([O:22]C(=O)C)[C:18]2=[O:26])[C:13]([I:27])=[C:12]([C:28]([NH:30][CH2:31][CH:32]([O:38]C(=O)C)[CH2:33][O:34]C(=O)C)=[O:29])[C:11]=1[I:42])=[O:9])(=O)C.C[O-].[Na+].CO.CCC1(C2C=CC(N)=CC=2)C(=O)NC(=O)CC1>O>[OH:4][CH:5]([CH2:43][OH:44])[CH2:6][NH:7][C:8]([C:10]1[C:15]([I:16])=[C:14]([N:17]2[CH2:21][CH2:20][CH:19]([OH:22])[C:18]2=[O:26])[C:13]([I:27])=[C:12]([C:28]([NH:30][CH2:31][CH:32]([OH:38])[CH2:33][OH:34])=[O:29])[C:11]=1[I:42])=[O:9]
Reactant: CC(=O)OCC(CNC(=O)c1c(I)c(C(=O)NCC(COC(C)=O)OC(C)=O)c(I)c(N2CCC(OC(C)=O)C2=O)c1I)OC(C)=O
Agent: CCC1(c2ccc(N)cc2)CCC(=O)NC1=O
Agent: C[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: O=C(NCC(O)CO)c1c(I)c(C(=O)NCC(O)CO)c(I)c(N2CCC(O)C2=O)c1I
Yield: 71.2 %

Procedure:
N,N'-Bis-[2,3-diacetyloxypropyl]-5-[3-acetyloxy-2-oxo-1-pyrrolidinyl]-2,4,6-triiodo-1,3-benzenedicarboxamide of example 5b (4.20 g, 4.20 mmol) was treated with a 0.105M solution of methanolic sodium methoxide [Prepared by the addition of Na metal (48 mg, 2.10 mmol) to dry methanol (20 ml)] under a nitrogen atmosphere for 2.5 hours. The pH was then adjusted to 6.70 using Dowex-50 resin (H+ form) and AG-1 (OH- form) as necessary. The resin was removed and the solvents evaporated to give a yellow oil. This product was dissolved in 20 ml of deionized water and the pH adjusted to 6.98 by the addition of AG-1 (OH- 1 form) resin. The resin was filtered off and the filtrate containing the crude product was purified by low pressure reverse phase column chromatography using a CHP-20 resin to obtain N,N'-bis-[2,3-dihydroxypropyl]-5-[3-hydroxy-2-oxo-1-pyrrolidinyl]- -2,4,6-triiodo-1,3-benzenedicarboxamide as a white foam (2.36 g, 71% yield).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:16]#[N:17].Cl.N1C=CC=CC=1.[NH2:25][C:26]1[CH:34]=[CH:33][C:29]([C:30]([NH2:32])=[O:31])=[CH:28][CH:27]=1>C(OCCO)C>[C:16]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[NH:25][C:26]1[CH:34]=[CH:33][C:29]([C:30]([NH2:32])=[O:31])=[CH:28][CH:27]=1)=[CH:10][C:9]([O:12][CH3:13])=[C:8]([O:14][CH3:15])[CH:7]=2)#[N:17]
Reactant: COc1cc2ncc(C#N)c(Cl)c2cc1OC
Reactant: NC(=O)c1ccc(N)cc1
Agent: Cl
Solvent: c1ccncc1
Solvent: CCOCCO
Product: COc1cc2ncc(C#N)c(Nc3ccc(C(N)=O)cc3)c2cc1OC
Yield: 73.4 %

Procedure:
Using an analogous procedure to that described in Example 286, 248.7 mg (1 mmol) of 4-chloro-6,7-dimethoxy-3-quinolinecarbonitrile in 10 mL of 2-ethoxyethanol and in the presence of 115.6 mg (1 mmol) of pyridine hydrochloride was reacted with 163.4 mg (1.2 mmol) of 4-amino-benzamide to give 255.7 mg (73.4%) of the product as a light yellow solid, m.p.>250° C., mass (electrospray, m/e): M+H 348.9.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[C:8]([C:9]([OH:11])=[O:10])=[CH:7][N:6]=[CH:5][CH:4]=1.[H][H]>CCO.[Pd]>[F:13][C:2]([F:1])([F:12])[C@H:3]1[CH2:4][CH2:5][NH:6][CH2:7][C@H:8]1[C:9]([OH:11])=[O:10]
Reactant: O=C(O)c1cnccc1C(F)(F)F
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: O=C(O)[C@@H]1CNCC[C@@H]1C(F)(F)F
Reaction time: 3 h
Yield: 100.2 %

Procedure:
A solution of 4-(trifluoromethyl)nicotinic acid (1.50 g, 7.85 mmol) in EtOH (78 mL) was passed through an H-cube™ equipped with a ThalesNano CatCart® 10 wt % Pd/C catalyst cartridge at about 1.0 mL/min, at about 80° C., under about 1305 psi of hydrogen. After about 3 h, the solvent was removed under reduced pressure to afford cis-4-(trifluoromethyl)piperidine-3-carboxylic acid (1.55 g, 100% crude): LC/MS (Table 1, Method b) Rt=0.54 min; MS m/z: 198 (M+H)+.
Reaction SMILES: [Si]([O:8][C:9]1[CH:10]=[CH:11][C:12]([N:32]2[C:36](=[O:37])[C:35]3=[CH:38][CH:39]=CC=[C:34]3[C:33]2=O)=[C:13]([CH:31]=1)[NH:14][C:15]([O:17][CH2:18][CH:19]1[CH2:24][CH2:23][N:22](C2C=CN=CC=2)[CH2:21][CH2:20]1)=[O:16])(C(C)(C)C)(C)C.[CH2:43]([Cl:45])Cl>NN.CO>[Cl:45][C:43]1[CH:39]=[CH:38][C:35]([C:36]([NH:32][C:12]2[C:13]([NH:14][C:15]([O:17][CH:18]([CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)[C:19]3[CH:20]=[CH:21][N:22]=[CH:23][CH:24]=3)=[O:16])=[CH:31][C:9]([OH:8])=[CH:10][CH:11]=2)=[O:37])=[CH:34][CH:33]=1
Reactant: ClCCl
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(N2C(=O)c3ccccc3C2=O)c(NC(=O)OCC2CCN(c3ccncc3)CC2)c1
Agent: NN
Solvent: CO
Product: O=C(Nc1cc(O)ccc1NC(=O)c1ccc(Cl)cc1)OC(c1ccncc1)C1CCNCC1
Yield: 86 %

Procedure:
A solution of 5-(tert-butyldimethylsilyloxy)-2-phthalimido-N-[[1-(4-pyridyl)piperidin-4-yl]methoxycarbonyl]aniline (1.34 g, 2.28 mmol) in 1 M hydrazine in methanol (6 mL) was stirred at ambient temperature for 40 h during which time a white precipitate formed. The mixture was further diluted with methylene chloride and cooled with an ice bath then filtered. The filtrate was washed once with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to yield 890 mg (86%) of the title compound as a tan powder.
Reaction SMILES: CC(OC(/N=N/C(OC(C)C)=O)=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:34]1([C:40]2[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[N:42]([S:49]([C:52]3[CH:57]=[CH:56][C:55]([CH3:58])=[CH:54][CH:53]=3)(=[O:51])=[O:50])[C:41]=2[CH:59](O)[CH3:60])[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C1(P([N:76]=[N+:77]=[N-:78])(C2C=CC=CC=2)=O)C=CC=CC=1>O1CCOCC1.C(Cl)Cl>[N:76]([CH:59]([C:41]1[N:42]([S:49]([C:52]2[CH:57]=[CH:56][C:55]([CH3:58])=[CH:54][CH:53]=2)(=[O:50])=[O:51])[C:43]2[C:48]([C:40]=1[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH3:60])=[N+:77]=[N-:78]
Reactant: Cc1ccc(S(=O)(=O)n2c(C(C)O)c(-c3ccccc3)c3ccccc32)cc1
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)n2c(C(C)N=[N+]=[N-])c(-c3ccccc3)c3ccccc32)cc1
Reaction time: 0.17 h
Yield: 75.2 %

Procedure:
A solution of DIAD (1.80 g, 8.89 mmol) in dioxane (5 mL) was added to a solution of triphenylphosphine (2.33 g, 8.89 mmol) in dioxane (20 mL) at 0° C. under a nitrogen atmosphere. After 10 min stirring, 1-[3-phenyl-1-(toluene-4-sulfonyl)-1H-indol-2-yl]ethanol (1.74 g, 4.44 mmol) in dioxane (15 mL) was added followed by diphenylphosphoryl azide (1.47 g, 5.53 mmol) in dioxane (5 mL). Stirring at 20° C. was continued for 16 h and then the crude reaction mixture was diluted with DCM and purified by column chromatography (Si—PCC, gradient 10-100% DCM in pentane) affording 2-(1-Azidoethyl)-3-phenyl-1-(toluene-4-sulfonyl)-1H-indole as a gum (1.39 g, 75%). LCMS: RT 4.77 min [M-N3]+ 374.1.
Reaction SMILES: [C:1]1(=[O:22])[N:5]([CH:6]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:7](O)=[O:8])[C:4](=[O:17])[C:3]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:2]12.O1CCCC1.[OH-].[NH4+:29]>O>[C:1]1(=[O:22])[N:5]([CH:6]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:7]([NH2:29])=[O:8])[C:4](=[O:17])[C:3]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:2]12
Reactant: O=C(O)C(Cc1ccccc1)N1C(=O)c2ccccc2C1=O
Reactant: [NH4+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: NC(=O)C(Cc1ccccc1)N1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 84 %

Procedure:
To a stirred solution of 2-phthalimido-3-phenylpropionic acid (2.95 g, 10.0 mmol) in tetrahydrofuiran (25 mL) are added carbonyldiimridazole (1.62 g, 10.0 mmol) and a few crystals of 4-N,N-dimethylaminopyridine, followed by 15 mL of tetrahydrofuran. The reaction mixture is stirred at room temperature for 45 minutes and 1 mL of concentrated ammonium hydroxide then is added. After 10 minutes, the reaction mixture is diluted with 50 mL water and the resulting slurry is partially concentrated to remove the tetrahydrofuran and filtered. The solid is washed with water and dried in vacuo (60° C., <1 mm) to afford 2.46 g (84%) of 2-phthalimido-3-phenylpropionamide as a white powder: mp 224°-226° C.; 1H NMR (DMSO-d6, 250 MHz) δ 7.79 (s, 4 H, Ar), 7.71 (br s, 1 H, CONH2), 7.32 (br s, 1 H, CONH2), 7.20-7.02 (m, 5H, Ar), 5.06-4.98 (m, 1H), 3.56-3.25 (m, 2H); 13C NMR (DMSO-d6, 250 MHz) d: 169.6, 168.0, 137.1, 134.3, 131.2, 129.5, 128.1, 126.3, 122.9, 54.2, 33.7. Anal. Calculated for C17H14N2O3. Theoretical: C, 69.38; H, 4.79; N, 9.52. Found: C, 69.37; H, 4.73; N, 9.43.
Reaction SMILES: [NH2:1][C:2]1[N:6]([CH:7]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH:8]([OH:10])[CH3:9])[CH:5]=[N:4][C:3]=1[C:17]#[N:18].[OH-].[K+].[SH2:21].C(O)(=O)C>CO.O>[NH2:1][C:2]1[N:6]([CH:7]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH:8]([OH:10])[CH3:9])[CH:5]=[N:4][C:3]=1[C:17](=[S:21])[NH2:18]
Reactant: CCCCCCC(C(C)O)n1cnc(C#N)c1N
Reactant: S
Agent: [K+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: O
Solvent: CO
Product: CCCCCCC(C(C)O)n1cnc(C(N)=S)c1N

Procedure:
A solution of erythro 5-amino-1-(2-hydroxynon-3-yl)-1H-imidazole-4-carbonitrile (1.02 g; 0.004 m) and potassium hydroxide (0.91 g; 0.163 m) in dry methanol (80 ml) was cooled to 0°, saturated with hydrogen sulphide, and heated to 100° for 5 hours. After cooling to 0°, nitrogen was passed through the solution to remove excess hydrogen sulphide and the residue was evaporated in vacuo to give a yellow solid. This solid was suspended in water and acetic acid added dropwise to pH5. The resulting precipitate was collected by filtration and washed with water. The residue was dissolved in dichloromethane/ethyl acetate, dried (Na2SO4) and evaporated in vacuo to give a white solid (1.22 g). Recrystallisation from ethyl acetate/charcoal gave a pale yellow solid, which was triturated in ether to give the product as white crystals (0.74 g) mp 170°-171°.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[CH:27]=[CH:26][C:7]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([NH:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])=[O:16])[CH2:11][CH2:10]2)=[CH:6][CH:5]=1.C([O:35][C:36]1[CH:46]=[CH:45][C:39]([O:40][CH2:41][C@@H:42]2[CH2:44][O:43]2)=[CH:38][CH:37]=1)C1C=CC=CC=1.CCCCCC>ClCCl.CO>[OH:43][C@H:42]([CH2:41][O:40][C:39]1[CH:45]=[CH:46][C:36]([OH:35])=[CH:37][CH:38]=1)[CH2:44][NH:1][CH2:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([NH:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])=[O:16])[CH2:11][CH2:10]2)=[CH:26][CH:27]=1
Reactant: c1ccc(COc2ccc(OC[C@@H]3CO3)cc2)cc1
Reactant: CCCCCCCCNC(=O)N1CCC(Oc2ccc(CCN)cc2)CC1
Solvent: ClCCl
Solvent: CCCCCC
Solvent: CO
Product: CCCCCCCCNC(=O)N1CCC(Oc2ccc(CCNC[C@H](O)COc3ccc(O)cc3)cc2)CC1

Procedure:
4-[4-(2-Aminoethyl)phenoxy]N-octyl-1-piperidinecarboxamide (0.825 g, 2.2 mmol) was reacted with (2S)-2-{[4-(benzyloxy)phenoxy]methyl}oxirane (0.564 g, 2.2 mmol) according to Procedure G (eluant: 33:1 going to 9:1 dichloromethane-methanol) to give the title compound following crystallization from hexane (0.533 g, 0.84 mmol).
Reaction SMILES: [Si]([O:8][CH:9]([CH2:25][CH2:26]O)[C@@H:10]([NH:14][C:15](=[O:24])[O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH:11]([CH3:13])[CH3:12])(C(C)(C)C)(C)C.C(N(CC)CC)C.CS(Cl)(=O)=O.C(OCC)(=O)C>C1COCC1>[OH:8][CH:9]1[CH2:25][CH2:26][N:14]([C:15]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)=[O:24])[C@H:10]1[CH:11]([CH3:12])[CH3:13]
Reactant: CC(C)[C@H](NC(=O)OCc1ccccc1)C(CCO)O[Si](C)(C)C(C)(C)C
Agent: CS(=O)(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Product: CC(C)[C@H]1C(O)CCN1C(=O)OCc1ccccc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 32.5 %

Procedure:
To a solution (188 mL) of benzyl ((1S)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-hydroxy-1-isopropylbutyl)carbamate (14.9 g) in dehydrated THF was added triethylamine (5.07 g) and a solution (10 mL) of methanesulfonyl chloride (4.96 g) in dehydrated THF was added dropwise to the mixture under ice-cooling. After stirring at the same temperature for 1 hr, the reaction mixture was poured into a mixture of ethyl acetate and ice water and then the mixture was partitioned. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. To a solution (188 mL) of the residue in dehydrated THF was added with stirring under ice-cooling 1 mol/L potassium tert-butoxide—THF solution (37.7 mL), and the mixture was stirred at the same temperature for 1 hr. The reaction mixture was poured into a mixture of ethyl acetate and ice water and the mixture was partitioned. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. To a solution (188 mL) of the residue in dehydrated THF was added with stirring under ice-cooling 1 mol/L tetrabutylammonium fluoride—THF solution (37.7 mL), and the mixture was stirred at the same temperature for 1 hr and at room temperature for 5 hr. The reaction mixture was poured into a mixture of ethyl acetate and ice water and then the mixture was partitioned. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate/19/1→2/3) to give benzyl (2S)-3-hydroxy-2-isopropylpyrrolidine-1-carboxylate as colorless oil (yield: 3.22 g).
Reaction SMILES: [C:1]([O:5][OH:6])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].[C:9](Cl)(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>O>[C:9]([O:6][O:5][C:1]([CH3:4])([CH3:3])[CH3:2])(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: CC(C)(C)OO
Reactant: O=C(Cl)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(C)(C)OOC(=O)c1ccccc1

Procedure:
The reaction is effected in a reactor arrangement of a first reactor of type D with two reactors of type B connected downstream in series. 1.72 kg/l·h of a 19.5% by weight solution of tert-butyl hydroperoxide and 9.5% by weight of sodium hydroxide in water and 0.49 kg/l·h of benzoyl chloride are fed to the first reactor. The metering rates are based on the total volume of the reactor arrangement in litres. Cooling with cooling water keeps the internal temperature in all reactors at 25° C. The organic phase is removed from the reaction mixture withdrawn from the third reactor, washed successively with an 8% by weight solution of sodium hydroxide in water, with a solution of 10% by weight of sodium sulphite in water comprising acetic acid and with demineralized water, and then dried with calcium chloride. 0.61 kg/l·h of tert-butyl peroxybenzoate is obtained (89.9% based on benzoyl chloride).