Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([CH2:4][CH:5]1[C:14]2[CH:15]=[CH:16][S:17][C:13]=2[C:12]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=2[O:6]1)([O-])=O.[NH4+].[Cl-]>CC(O)=O.[Fe]>[S:17]1[C:13]2[C:12]3[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=3[O:6][CH:5]([CH2:4][NH2:1])[C:14]=2[CH:15]=[CH:16]1
Reactant: O=[N+]([O-])CC1Oc2ccccc2-c2sccc21
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CC(=O)O
Product: NCC1Oc2ccccc2-c2sccc21
Reaction time: 8 h
Yield: 94.6 %

Procedure:
To a solution of 4-(nitromethyl)-4H-thieno[3,2-c]chromene (2.5 g, 10.7 mmol) in AcOH (20 mL) was added NH4Cl (5.4 g, 100 mmol) and Fe (2.8 g, 50 mmol). After stirring overnight, the reaction mixture was filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography to give the title compound (2.2 g, 96%).
Reaction SMILES: [CH3:1][S:2][CH2:3][CH2:4][CH2:5][CH2:6][OH:7].[N+:8]([C:11]1[CH:18]=[CH:17][CH:16]=[C:15]([N+]([O-])=O)[C:12]=1[C:13]#[N:14])([O-:10])=[O:9]>>[CH3:1][S:2][CH2:3][CH2:4][CH2:5][CH2:6][O:7][C:15]1[CH:16]=[CH:17][CH:18]=[C:11]([N+:8]([O-:10])=[O:9])[C:12]=1[C:13]#[N:14]
Reactant: CSCCCCO
Reactant: N#Cc1c([N+](=O)[O-])cccc1[N+](=O)[O-]
Product: CSCCCCOc1cccc([N+](=O)[O-])c1C#N
Yield: 89 %

Procedure:
Prepared as in Example 215c from 4-(methylthio)butan-1-ol and 2,6-dinitrobenzonitrile in 89% yield. MS 267 (MH+).
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[C:3]1[CH:4]=[C:5]([N:13]=[C:14]=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH2:18]([CH:20]([NH:23][OH:24])[CH2:21][CH3:22])[CH3:19]>>[OH:24][N:23]([CH:20]([CH2:21][CH3:22])[CH2:18][CH3:19])[C:14]([NH:13][C:5]1[CH:4]=[C:3]([C:2]([F:16])([F:17])[F:1])[CH:8]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:6]=1)=[O:15]
Reactant: O=C=Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: CCC(CC)NO
Product: CCC(CC)N(O)C(=O)Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Yield: 8.8 %

Procedure:
Using the method of Compound 72, 3,5-bis(trifluoromethyl)phenylisocyanate (1.3 g, 5.1 mmole) was reacted with N-(1-ethylpropyl)hydroxylamine (0.58 g, 5.6 mmole) to provide 160 mg of the desired product as a white crystalline solid, m.p. 115°-116° C. Analysis: Calculated for: C14H16F6N2O2 : %C, 46.93; %H, 4.5; %N, 7.82; Found: %C, 46.8; %H, 4.37; %N, 7.89.
Reaction SMILES: CC[C@@]1(O)C(=O)[O:7]CC2C(N3C(=CC1=2)C1N=C2C(C=CC=C2)=CC=1C3)=O.C(O)(=O)C1C=CC=CC=1.[CH2:36]1[CH2:41][CH2:40][CH:39]([N:42]=[C:43]=[N:44][CH:45]2[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]2)[CH2:38][CH2:37]1>CN(C1C=CN=CC=1)C.CN(C=O)C>[CH:45]1([NH:44][C:43](=[O:7])[NH:42][CH:39]2[CH2:38][CH2:37][CH2:36][CH2:41][CH2:40]2)[CH2:50][CH2:49][CH2:48][CH2:47][CH2:46]1
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: CC[C@@]1(O)C(=O)OCc2c1cc1n(c2=O)Cc2cc3ccccc3nc2-1
Agent: CN(C)c1ccncc1
Agent: O=C(O)c1ccccc1
Solvent: CN(C)C=O
Product: O=C(NC1CCCCC1)NC1CCCCC1
Temperature: 25 °C
Reaction time: 72 h
Yield: 38 %

Procedure:
Camptothecin (0.8 g, 0.0023 mol), benzoic acid (1.8 g, 0.014 mol), DCC (1.2 g, 0.0058 mol), and DMAP (0.3 g, 0.0025 mol) were added to 60 ml DMF in a 250 ml round-bottomed flask equipped with a mechanical stirrer. The mixture was stirred under N2 at room temperature for 72 hr. Dicyclohexyl urea formed during the reaction was removed by filtration. The filtrate was poured onto 600 ml ice water while stirring. The stirring was maintained for 30 min. The crude product was collected by filtration. The residue was chromatographically separated with THF-CH2Cl2 (1:15) as eluent. The pure product (0.4 g) was obtained as white powders by precipitation from petroleum ether. Yield 38%. Mass m/e (relative intensity): 452 (m+, 25), 330 (100), 315 (35), 302 (60), 287 (40), 169 (12), 122 (36), 105 (70), 77 (35), 69 (26); precise mass (C27H20N2O5): found, 452,137; required, 452.137.
Reaction SMILES: Br[CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=O.[C:12]1(=[O:30])[N:16]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22](=[S:24])[NH2:23])[C:15](=[O:25])[C:14]2=[CH:26][CH:27]=[CH:28][CH:29]=[C:13]12>>[C:15]1(=[O:25])[N:16]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]2[S:24][C:2]3[CH2:10][C:9]4[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=4[C:3]=3[N:23]=2)[C:12](=[O:30])[C:13]2=[CH:29][CH:28]=[CH:27][CH:26]=[C:14]12
Reactant: NC(=S)CCCCCN1C(=O)c2ccccc2C1=O
Reactant: O=C1c2ccccc2CC1Br
Product: O=C1c2ccccc2C(=O)N1CCCCCc1nc2c(s1)Cc1ccccc1-2

Procedure:
2-Bromo-1-indanone, 6-phthalimidohexanethioamide
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([NH2:11])[S:9][CH:10]=1)=[O:5])[CH3:2].[Br:12]N1C(=O)CCC1=O>C(#N)C>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([NH2:11])[S:9][C:10]=1[Br:12])=[O:5])[CH3:2]
Reactant: O=C1CCC(=O)N1Br
Reactant: CCOC(=O)c1csc(N)n1
Solvent: CC#N
Product: CCOC(=O)c1nc(N)sc1Br
Reaction time: 3 h

Procedure:
2-Amino-thiazole-4-carboxylic acid ethyl ester (1.4 g, 8 mmol) is dissolved in acetonitrile (15 ml) and N-bromosuccinimide. (1.7 g, 9.6 mmol, 1.2 equiv.) was added in one portion. The mixture was stirred at room temp. for 3 hours, then filtered and the filtrate was evaporated. After purification on silica-gel with ethyl acetate/n-heptane as eluent, 0.71 g of an off-white solid were obtained: MS: m/e 248.9 (M−H).
Reaction SMILES: [CH2:1]([C:5]1[C:6](=[O:20])[NH:7][CH2:8][CH2:9][CH2:10][C:11]=1[C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=1)[C:2]([CH3:4])=[O:3].[CH2:21](O)[CH2:22][OH:23].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>C1C=CC=CC=1.O>[CH2:21]1[CH2:22][O:23][CH2:4][CH:2]([CH2:1][C:5]2[C:6](=[O:20])[NH:7][CH2:8][CH2:9][CH2:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=2)[O:3]1
Reactant: OCCO
Reactant: COc1cccc(C2=C(CC(C)=O)C(=O)NCCC2)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccccc1
Solvent: O
Product: COc1cccc(C2=C(CC3COCCO3)C(=O)NCCC2)c1

Procedure:
The starting material is prepared as follows: The solution of 27.2 g of 3-acetonyl-4-(3-methoxyphenyl)-1,5,6,7-tetrahydro-2H-azepinone, 31 g of ethylene glycol and 0.2 g of p-toluene-sulfonic acid hydrate in 200 ml of benzene is refluxed with a water separator for 7 hours. It is cooled to 0°, 100 ml of 5% aqueous sodium bicarbonate are added and the benzene layer separated. It is washed with water, dried, evaporated and the residue crystallized from diethyl ether to give the 3-(2-ethylenedioxypropyl)-4-(3-methoxyphenyl)-1,5,6,7-tetrahydro-2H-azepinone melting at 132°-134°.
Reaction SMILES: [C:1](Cl)(Cl)=[O:2].[NH2:5][C:6]1[C:7]([F:19])=[CH:8][C:9]([Cl:18])=[C:10]([NH:12][S:13]([CH2:16][Cl:17])(=[O:15])=[O:14])[CH:11]=1>C(C(C)=O)C(C)C>[Cl:17][CH2:16][S:13]([NH:12][C:10]1[CH:11]=[C:6]([N:5]=[C:1]=[O:2])[C:7]([F:19])=[CH:8][C:9]=1[Cl:18])(=[O:15])=[O:14]
Reactant: Nc1cc(NS(=O)(=O)CCl)c(Cl)cc1F
Reactant: O=C(Cl)Cl
Solvent: CC(=O)CC(C)C
Product: O=C=Nc1cc(NS(=O)(=O)CCl)c(Cl)cc1F
Temperature: 35 °C

Procedure:
To a stirred solution of 218 g (2.2 mole) of phosgene in 0.6 L of methyl isobutyl ketone at 0° C. was added 546.2 g (2 mol) of N-(5-amino-2-chloro-4-fluorophenyl)-1-chloromethanesulfonamide dissolved in 2 L of methyl isobutyl ketone. During the addition (75 minutes) the temperature was kept between −3° C. and 3° C. The temperature of the solution was raised to 35° C. and 1 L of the solvent was distilled off under reduced pressure (11.0-11.5 kPa (110-115 mbar), maximum temperature: 60° C.). This isocyanate solution was used in the next step without further purification.
Reaction SMILES: [CH2:1]([O:9][CH2:10][C:11](Cl)=[O:12])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[NH2:14][C:15]1[C:20]([C:21]#[N:22])=[CH:19][CH:18]=[CH:17][N:16]=1>CN(C1C=CN=CC=1)C.ClCCl.N1C=CC=CC=1>[C:21]([C:20]1[C:15]([NH:14][C:11](=[O:12])[CH2:10][O:9][CH2:1][CH2:2][C:3]2[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=2)=[N:16][CH:17]=[CH:18][CH:19]=1)#[N:22]
Reactant: O=C(Cl)COCCc1ccccc1
Reactant: N#Cc1cccnc1N
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: N#Cc1cccnc1NC(=O)COCCc1ccccc1
Reaction time: 3 h

Procedure:
Phenethyloxy-acetyl chloride (3.79 g, 6.12 mmol) was added to a solution of 2-amino-3-cyanopyridine ([24517-64-4], 662 mg, 5.56 mmol) and DMAP (67 mg, 0.55 mmol) in a mixture of dichloromethane (8 ml) and pyridine (8 ml). After 3 h at r.t., the solvent was evaporated, and N-(3-cyano-pyridin-2-yl)-2-phenethyloxy-acetamide was isolated from the residue by column chromatography (silica gel, heptane, ethyl acetate, methanol). MS: m/e=282.1 [M+H+], 1H NMR (d6-DMSO): 2.91 (t, 2H), 3.77 (t, 2H), 4.18 (s, 2H), 7.17-7.23 (m, 5H), 7.47 (dd, 1H), 8.37 (d, 1H), 8.71 (d, 1H), 10.55 (bs, 1H).
Reaction SMILES: [H-].[Na+].CN(C)C=O.[OH:8][C:9]1[CH:10]=[C:11]([CH:20]=[CH:21][CH:22]=1)[C:12]([N:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)=[O:13].Br[CH2:24][CH2:25][CH2:26][N:27]1[C:31](=[O:32])[C:30]2=[CH:33][CH:34]=[CH:35][CH:36]=[C:29]2[C:28]1=[O:37]>O>[O:37]=[C:28]1[C:29]2[C:30](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31](=[O:32])[N:27]1[CH2:26][CH2:25][CH2:24][O:8][C:9]1[CH:10]=[C:11]([CH:20]=[CH:21][CH:22]=1)[C:12]([N:14]1[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1)=[O:13]
Reactant: O=C1c2ccccc2C(=O)N1CCCBr
Reactant: O=C(c1cccc(O)c1)N1CCCCC1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C(c1cccc(OCCCN2C(=O)c3ccccc3C2=O)c1)N1CCCCC1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
To a suspension of 0.09 g. (0.0024 mole) of 60% sodium hydride in 10 ml. of dry N,N-dimethylformamide is added dropwise over 5 minutes a solution of 0.5 g. (0.0024 mole) of 1-(3-hydroxybenzoyl)piperidine, prepared according to the method of G. Tilly, Chem. Ther. 2 (1), 57-65 (1967); C. A. 67 32432S, in 10 ml. of dry N,N-dimethylformamide. The mixture is stirred at room temperature for 5 minutes and then 0.64 g. (0.0024 mole) of N-(3-bromopropyl)phthalimide is added. The mixture is stirred at room temperature for 1 hour and is diluted with water to the cloudy point. The precipitate which forms is collected and is air dried to give 0.5 g. of product. A small amount is recrystallized from ethanol to give the analytical sample, m.p. 120°-122° C.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([N:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:11]([C:20]([F:23])([F:22])[F:21])=[CH:10][C:9]=1[NH:24][C:25](=[O:48])[CH2:26][C:27](=O)[C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([C:34]2[CH:38]=[C:37]([CH2:39][O:40]C3CCCCO3)[O:36][N:35]=2)[CH:29]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[OH:40][CH2:39][C:37]1[O:36][N:35]=[C:34]([C:30]2[CH:29]=[C:28]([C:27]3[CH2:26][C:25](=[O:48])[NH:24][C:9]4[CH:10]=[C:11]([C:20]([F:21])([F:22])[F:23])[C:12]([N:14]5[CH2:19][CH2:18][O:17][CH2:16][CH2:15]5)=[CH:13][C:8]=4[N:7]=3)[CH:33]=[CH:32][CH:31]=2)[CH:38]=1
Reactant: CC(C)(C)OC(=O)Nc1cc(N2CCOCC2)c(C(F)(F)F)cc1NC(=O)CC(=O)c1cccc(-c2cc(COC3CCCCO3)on2)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C1CC(c2cccc(-c3cc(CO)on3)c2)=Nc2cc(N3CCOCC3)c(C(F)(F)F)cc2N1

Procedure:
The title compound was prepared from (RS)-[5-morpholin-4-yl-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M31) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a white solid (386 mg).
Reaction SMILES: F[C:2]1(F)[C:10]2[C:5](=[C:6]([F:14])[C:7]([F:13])=[C:8]([F:12])[C:9]=2[F:11])[C:4](=[O:15])[O:3]1.C(O)(=[O:19])C>>[F:11][C:9]1[C:8]([F:12])=[C:7]([F:13])[C:6]([F:14])=[C:5]2[C:4](=[O:15])[O:3][C:2](=[O:19])[C:10]=12
Reactant: O=C1OC(F)(F)c2c(F)c(F)c(F)c(F)c21
Reactant: CC(=O)O
Product: O=C1OC(=O)c2c(F)c(F)c(F)c(F)c21
Yield: 87.5 %

Procedure:
Into a 300 ml glass reactor equipped with a reflux condenser and a stirrer, 100 g (0.413 mol) of the 3,3,4,5,6,7-hexafluoro-1-[3H]-isobenzofuranone obtained in Example 2, and 100 ml of acetic acid were charged, and the mixture was reacted for 48 hours under reflux. Then, the reaction mixture was separated by distillation to obtain 79.5 g of tetrafluorophthalic anhydride. The yield was 87.5%.
Reaction SMILES: [CH2:1]([C:3]1[N:4]=[C:5]([CH2:55][CH2:56][CH3:57])[N:6]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:31]3[N:35](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:34]=[N:33][N:32]=3)=[CH:21][CH:20]=2)[C:7]=1[C:8]([O:10][CH2:11][O:12][C:13](=[O:17])[CH:14]([CH3:16])[CH3:15])=[O:9])[CH3:2].C(O)(=O)C>CO>[CH2:1]([C:3]1[N:4]=[C:5]([CH2:55][CH2:56][CH3:57])[N:6]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:31]3[NH:32][N:33]=[N:34][N:35]=3)=[CH:21][CH:20]=2)[C:7]=1[C:8]([O:10][CH2:11][O:12][C:13](=[O:17])[CH:14]([CH3:15])[CH3:16])=[O:9])[CH3:2]
Reactant: CCCc1nc(CC)c(C(=O)OCOC(=O)C(C)C)n1Cc1ccc(-c2ccccc2-c2nnnn2C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CC(=O)O
Solvent: CO
Product: CCCc1nc(CC)c(C(=O)OCOC(=O)C(C)C)n1Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 79.8 %

Procedure:
To a solution of 0.46 g isobutyryloxymethyl 4-ethyl-2-propyl-1-[[2'-(N-triphenylmethyl(tetrazol-5-yl))biphenyl-4-yl]methyl]imidazole-5-carboxylate in 10 mL MeOH was added 1 5 mL glacial acetic acid and the mixture stirred 2 days at room temperature. The reaction was evaporated to near dryness and the residue purified by flash chromatography using a 0% to 5% MeOH/CHCl3 gradient. There was obtained 0.250 g of the title compound.
Reaction SMILES: [Cl:1][C:2]([CH3:25])([CH3:24])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C:18](=[O:23])[C:19]([Cl:22])([CH3:21])[CH3:20])=[CH:14][CH:13]=2)=[CH:7][CH:6]=1)=[O:4].[Br:26]Br>ClC1C=CC=CC=1Cl>[Br:26][CH:11]([C:12]1[CH:17]=[CH:16][C:15]([C:18](=[O:23])[C:19]([Cl:22])([CH3:20])[CH3:21])=[CH:14][CH:13]=1)[C:8]1[CH:7]=[CH:6][C:5]([C:3](=[O:4])[C:2]([Cl:1])([CH3:25])[CH3:24])=[CH:10][CH:9]=1
Reactant: CC(C)(Cl)C(=O)c1ccc(Cc2ccc(C(=O)C(C)(C)Cl)cc2)cc1
Reactant: BrBr
Solvent: Clc1ccccc1Cl
Product: CC(C)(Cl)C(=O)c1ccc(C(Br)c2ccc(C(=O)C(C)(C)Cl)cc2)cc1
Temperature: 150 °C

Procedure:
A 350 ml sulfonation flask fitted with stirrer, reflux condenser and pressure equalized dropping funnel is charged with 2-chloro-1-{4-[4-(2-chloro-2-methyl-propionyl)-benzyl]-phenyl}-2-methyl-propan-1-one (113.1 g, 0.3 mol) and ortho-dichlorobenzene (150 ml). The mixture is heated to 150° C., and then a solution of bromine (49.6 g, 0.3 mol) in ortho-dichlorobenzene (50 ml) is added slowly in such a way that the bromine is reacted before the addition of the next drop of the bromine solution. When all the bromine has been added, the mixture is kept at 150° C. for another ten minutes, and then the ortho-dichlorobenzene is carefully removed on the rotavapor. The residue is recrystallized from hexanes to give the product (116.3 g, 85% of theory) as off white crystals, mp.=93° C. 1H-NMR (CDCl3, 400 MHz) δ 1.89 (s, 12 H, CH3); 6.29 (s, 1 H, CH); 7.54 (m, 4 H, H-4); 7.73 (m, 4 H, H-3). 13C-NMR (CDCl3, 100 MHz) δ 30.47 (C-8); 52.82 (C-1), 68.30 (C-7) 128.22 (C-3), 130.57 (C-4), 134.19 (C-5); 144.54 (C-2); 198.26 (C-6).
Reaction SMILES: [C:1]([Si:5]([CH3:42])([CH3:41])[O:6][CH:7]([C:17]1[C:18]([CH3:40])=[N:19][O:20][C:21]=1[C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:33]=[CH:32][C:31]([C:34]3([C:37]([OH:39])=O)[CH2:36][CH2:35]3)=[CH:30][CH:29]=2)=[CH:24][CH:23]=1)[CH2:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:43][C:44]1[CH:45]=[CH:46][C:47]([S:50]([NH2:53])(=[O:52])=[O:51])=[CH:48][CH:49]=1>>[C:1]([Si:5]([CH3:42])([CH3:41])[O:6][CH:7]([C:17]1[C:18]([CH3:40])=[N:19][O:20][C:21]=1[C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:29]=[CH:30][C:31]([C:34]3([C:37]([NH:53][S:50]([C:47]4[CH:48]=[CH:49][C:44]([CH3:43])=[CH:45][CH:46]=4)(=[O:51])=[O:52])=[O:39])[CH2:36][CH2:35]3)=[CH:32][CH:33]=2)=[CH:24][CH:23]=1)[CH2:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1noc(-c2ccc(-c3ccc(C4(C(=O)O)CC4)cc3)cc2)c1C(CCCc1ccccc1)O[Si](C)(C)C(C)(C)C
Reactant: Cc1ccc(S(N)(=O)=O)cc1
Product: Cc1ccc(S(=O)(=O)NC(=O)C2(c3ccc(-c4ccc(-c5onc(C)c5C(CCCc5ccccc5)O[Si](C)(C)C(C)(C)C)cc4)cc3)CC2)cc1

Procedure:
Prepared according to the procedure described in Example 315 using 1-(4′-{4-[1-(tert-butyl-dimethyl-silanyl oxy)-4-phenyl-butyl]-3-methyl-isoxazol-5-yl}-biphenyl-4-yl)-cyclopropanecarboxylic acid and p-toluenesulfonamide.
Reaction SMILES: FC(F)(F)[C:3]([N:5]([CH:7]1[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9][CH2:8]1)C)=O>Cl.O>[CH3:3][NH:5][C@H:7]1[CH2:12][CH2:11][C@H:10]([OH:13])[CH2:9][CH2:8]1
Reactant: CN(C(=O)C(F)(F)F)C1CCC(O)CC1
Agent: Cl
Solvent: O
Product: CN[C@H]1CC[C@H](O)CC1

Procedure:
2 g of 2,2,2-trifluoro-N-(4-hydroxy-cyclohexyl)-N-methyl-acetamide (149) were suspended in 10 mL of 1 N HCl and heated in a microwave at 150° until conversion was complete. The resulting solution was lyophilized and the residue was taken up in water and lyophilized again, twice to yield 1.45 g of 4-methylamino-cyclohexanol (150). Rt=0.13 min (Method C). Detected mass: 130.3 (M+H+).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[C:13]1[CH2:18][CH2:17][C:16](=O)[CH2:15][CH:14]=1)([O-:3])=[O:2].CC(O)=O.Cl.[CH3:25][NH2:26].[OH-].[Na+]>ClCCCl>[CH3:25][NH:26][CH:16]1[CH2:17][CH2:18][C:13]([C:7]2[C:6]3[C:10](=[CH:11][CH:12]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[NH:9][CH:8]=2)=[CH:14][CH2:15]1
Reactant: CN
Reactant: O=C1CC=C(c2c[nH]c3ccc([N+](=O)[O-])cc23)CC1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCCl
Solvent: CC(=O)O
Product: CNC1CC=C(c2c[nH]c3ccc([N+](=O)[O-])cc23)CC1
Reaction time: 14 h
Yield: 99.9 %

Procedure:
A solution of compound 79 (0.07 g, 0.273 mmol) in 1,2-dichloroethane (3 mL) was treated with AcOH (0.015 mL, 0.273 mmol), methylamine hydrochloride (0.018 g, 0.273 mmol), NaBH(OAC)3 (0.086 g, 0.409 mmol) at room temperature and stirred for over night (14 h). The reaction was basified with 2 N NaOH (25 mL) and product was extracted into ethyl acetate (2×20 mL). The combined ethyl acetate layer was washed with brine (15 mL) and dried (Na2SO4). Solvent was evaporated and crude was purified by column chromatography (2 M NH3 in methanol: CH2Cl2, 1:9) to obtain compound 80 (0.074 g, quantitative) as a solid. mp 208-210° C.; 1H NMR (DMSO-d6) δ 1.44-1.53 (m, 1H), 1.97-2.01 (m, 2H), 2.35 (s, 3H), 2.40-2.57 (m, 3H), 2.60-2.70 (m, 1H), 6.13 (brs, 1H), 7.54 (d, 1H, J=9.0 Hz), 7.63 (s, 1H), 8.00 (d, 1H, J=7.5 Hz), 8.67 (s, 1H), 11.85 (brs, 1H); ESI-MS m/z (%): 272 (M+, 100).
Reaction SMILES: [CH:1]1([C:7]2[C:8]3[S:20][C:19]([C:21]([O:23]C)=[O:22])=[CH:18][C:9]=3[NH:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].S(OC)(O[CH3:31])(=O)=O.[OH-].[Na+]>C1COCC1.CO>[CH:1]1([C:7]2[C:8]3[S:20][C:19]([C:21]([OH:23])=[O:22])=[CH:18][C:9]=3[N:10]([CH3:31])[C:11]=2[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: COC(=O)c1cc2[nH]c(-c3ccccc3)c(C3CCCCC3)c2s1
Reactant: COS(=O)(=O)OC
Agent: [H-]
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: Cn1c(-c2ccccc2)c(C2CCCCC2)c2sc(C(=O)O)cc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 42 %

Procedure:
A solution (0.1 M) of methyl 6-cyclohexyl-5-phenyl-4H-thieno[3,2-b]pyrrole-2-carboxylate in THF at 0° C. was treated with NaH (4 eq., 60% dispersion in mineral oil), and the suspension was stirred at RT for 30 min then it was treated dimethyl sulfate (3 eq.). The mixture was stirred at RT for 2 h then it was quenched with water and extracted with AcOEt. The combined organic phase was washed with aqueous NaHCO3 (saturated solution) then dried. Evaporation of the solvent gave a residue that was dissolved in MeOH. The resulting solution (0.13 M) was treated with aqueous NaOH (2 N solution, 8 eq.) then the mixture was heated to reflux for 2 h. After cooling down, the mixture was concentrated and the residue was purified by RP-HPLC (Conditions: Waters X-TERRA MS C18, 5 micron, 19×150 mm; flow: 18 mL/min; Gradient: A: H2O+0.05% TFA; B: MeCN+0.05% TFA; 95% A linear to 90% A in 2 min, linear to 60% A in 2 min, linear to 40% in 2 min, linear to 30% A in 2 min, linear to 0% A in 2 min) to afford the title compound (42%) as a solid.
Reaction SMILES: [C:1](Cl)(Cl)=[O:2].Cl.[CH2:6]([O:8][C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]=1[CH:19]([OH:25])[C:20](=[NH:24])[O:21]CC)[CH3:7].O1CCCC1>C1(C)C=CC=CC=1>[CH2:6]([O:8][C:9]1[CH:18]=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]=1[CH:19]1[O:25][C:1](=[O:2])[NH:21][C:20]1=[O:24])[CH3:7]
Reactant: O=C(Cl)Cl
Reactant: CCOC(=N)C(O)c1c(OCC)ccc2ccccc12
Agent: Cl
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CCOc1ccc2ccccc2c1C1OC(=O)NC1=O

Procedure:
By the procedure of Example 3, using a reaction time of 64 hours at room temperature following the cold phosgene perfusion, ethyl 1-(2-ethoxy-1-naphthyl)-1-hydroxymethanecarboximidate hydrochloride (5.0 g., 16.1 mmoles) in 200 ml. of tetrahydrofuran was converted to toluene recrystallized 5-(2-ethoxy-1-naphthyl)oxazolidine-2,4-dione (0.57 g., m.p. 221°-224° C., m/e 271).
Reaction SMILES: C1([ClH]P([ClH]C2C=CC=CC=2)(Cl)=O)C=CC=CC=1.[OH:18][C@@H:19]([C@H:21]1[C:42](=[O:43])[N:23]2[CH:24]([C:29]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=3)=[O:30])[C:25](=O)[C@H:26]([CH3:27])[C@H:22]12)[CH3:20].[SH:44][C@@H:45]1[CH2:49][N:48]([C:50]([O:52][CH2:53][C:54]2[CH:59]=[CH:58][C:57]([N+:60]([O-:62])=[O:61])=[CH:56][CH:55]=2)=[O:51])[C@H:47]([C:63]([N:65]2[CH2:68][CH:67]([NH:69][C:70]([O:72][CH2:73][C:74]3[CH:79]=[CH:78][C:77]([N+:80]([O-:82])=[O:81])=[CH:76][CH:75]=3)=[O:71])[CH2:66]2)=[O:64])[CH2:46]1>C(#N)C.C(OCC)(=O)C>[N+:80]([C:77]1[CH:76]=[CH:75][C:74]([CH2:73][O:72][C:70]([NH:69][CH:67]2[CH2:66][N:65]([C:63]([C@@H:47]3[CH2:46][C@H:45]([S:44][C:25]4[C@H:26]([CH3:27])[C@@H:22]5[C@@H:21]([C@H:19]([OH:18])[CH3:20])[C:42](=[O:43])[N:23]5[C:24]=4[C:29]([O:31][CH2:32][C:33]4[CH:34]=[CH:35][C:36]([N+:39]([O-:41])=[O:40])=[CH:37][CH:38]=4)=[O:30])[CH2:49][N:48]3[C:50]([O:52][CH2:53][C:54]3[CH:59]=[CH:58][C:57]([N+:60]([O-:62])=[O:61])=[CH:56][CH:55]=3)=[O:51])=[O:64])[CH2:68]2)=[O:71])=[CH:79][CH:78]=1)([O-:82])=[O:81]
Reactant: O=C(NC1CN(C(=O)[C@@H]2C[C@H](S)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)C1)OCc1ccc([N+](=O)[O-])cc1
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)C(=O)[C@H](C)[C@H]12
Solvent: CCOC(C)=O
Solvent: CC#N
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(S[C@H]3C[C@@H](C(=O)N4CC(NC(=O)OCc5ccc([N+](=O)[O-])cc5)C4)N(C(=O)OCc4ccc([N+](=O)[O-])cc4)C3)[C@H](C)[C@H]12
Reaction time: 1 h
Yield: 32.3 %

Procedure:
167 μl of diphenylphosphoric acid chloride and 140 μl of ditsopropylethylamine were added dropwise at the same time, whilst ice-cooling, to a solution of 278 mg of 4-nitrobenzyl (1R,5R,6S)-6-[(1R)-1-hydroxyethyl]-1-methyl-2-oxo-1-carbapenam-3-carboxylate in 4 ml of dry acetonitrile, and the resulting mixture was stirred at the same temperature for 1 hour. At the end of this time, a solution of 430 mg of (2S,4S)-4-mercapto-2-[3-(4-nitrobenzyloxycarbonylamino)azetidin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (prepared as described in Preparation 113) in 4 ml of dry acetonitrile and 134 μl of ditsopropylethylamine were added dropwise at the same time to the mixture, whilst ice-cooling. The resulting mixture was then stirred at the same temperature for 2 hours, after which it was left to stand overnight whilst ice-cooling. The reaction mixture was then diluted with ethyl acetate and washed with water and with an aqueous solution of sodium chloride. The ethyl acetate layer was dehydrated over anhydrous magnesium sulfate and then concentrated by evaporation under reduced pressure. The resulting residue was subjected to silica gel column chromatography, and the fractions obtained by elution with a 98:2 by volume mixture of ethyl acetate and methanol were combined and concentrated by evaporation under reduced pressure, to give 224 mg of the title compound, as a powder.