Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C([O-])([O-])=O.[K+].[K+].[C:17]([O:21][C:22](=[O:47])[CH2:23][N:24]1[C:28]2[CH:29]=[CH:30][C:31]([NH:33][S:34]([C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=3)(=[O:36])=[O:35])=[CH:32][C:27]=2[N:26]=[C:25]1[CH2:44][CH2:45][CH3:46])([CH3:20])([CH3:19])[CH3:18]>CC#N.CCOC(C)=O.O>[C:17]([O:21][C:22](=[O:47])[CH2:23][N:24]1[C:28]2[CH:29]=[CH:30][C:31]([N:33]([S:34]([C:37]3[CH:38]=[CH:39][C:40]([F:43])=[CH:41][CH:42]=3)(=[O:35])=[O:36])[CH2:2][CH2:3][CH2:4][C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=3)=[CH:32][C:27]=2[N:26]=[C:25]1[CH2:44][CH2:45][CH3:46])([CH3:20])([CH3:19])[CH3:18]
Reactant: CCCc1nc2cc(NS(=O)(=O)c3ccc(F)cc3)ccc2n1CC(=O)OC(C)(C)C
Reactant: BrCCCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Solvent: CCOC(C)=O
Product: CCCc1nc2cc(N(CCCc3ccccc3)S(=O)(=O)c3ccc(F)cc3)ccc2n1CC(=O)OC(C)(C)C
Temperature: 80 °C
Reaction time: 8 h

Procedure:
1-Bromo-3-phenylpropane (0.27 mmol) and K2CO3 (63 mg, 0.45 mmol) were added to a solution of [5-(4-fluoro-benzenesulfonylamino)-2-propyl-benzoimidazol-1-yl]-acetic acid tert-butyl ester (40 mg, 0.09 mmol) in CH3CN (1 mL), and stirred overnight at 80° C. The reaction mixture was diluted with EtOAc and H2O, and then filtered through an Extrelut column. The column was washed with EtOAc, and the filtrate was concentrated. The crude product was carried onto the next reaction without any further purification or characterization.
Reaction SMILES: P([O-])([O-])([O-])=O.[K+].[K+].[K+].N[C@H:10]([C:16]([OH:18])=[O:17])[CH2:11][CH2:12][CH2:13][CH2:14][NH2:15].C([O-])(=[O:21])C.Cl.CN1C2C=CC=CC=2SC1=NN>>[O:21]=[C:10]([CH2:11][CH2:12][CH2:13][CH2:14][NH2:15])[C:16]([OH:18])=[O:17]
Reactant: NCCCC[C@H](N)C(=O)O
Reactant: CC(=O)[O-]
Agent: Cl
Agent: Cn1c(=NN)sc2ccccc21
Agent: O=P([O-])([O-])[O-]
Product: NCCCCC(=O)C(=O)O
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
The activity of the present enzyme was measured in accordance with Soda's method (Analytical Biochemistry Vol. 25, p. 228, 1968) in the following manner. A reaction mixture consisting of 0.7 ml of 0.1 M potassium phosphate buffer (pH 8.0), 0.1 ml of catalase (750 U/ml), 0.1 ml of 0.1 M L-lysine solution and 0.1 ml of the present enzyme solution was incubated at 37° C. for 20 minutes with gentle shaking. After the incubation the reaction was terminated by the addition of 0.1 ml of 25% trichloroacetic acid. To the resulting reaction mixture were added 1.9 ml of 1 M acetate buffer (pH 5.0) and 0.8 ml of 0.1% 3-methyl-2-benzothiazolone hydrazone hydrochloride solution. The mixture was further incubated at 30° C. for 30 minutes and then allowed to cool to room temperature, after which measurement of optical density at 318 nm was carried out. The formed α-keto-ε -aminocaproic acid thus formed was determined from the resulting calibration curve. One unit of the enzyme was defined as the quantity of the enzyme catalyzing the formation of 1 μmol of α-keto-ε-aminocaproic acid at 37° C. per minute. The relative activity of the enzyme was also assayed by manometric and polarographic determination of the oxygen consumption.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[CH:3]=1.C([Li])(C)(C)C.[CH3:14][C:15]1([CH3:46])[CH:24]=[C:23](OS(C(F)(F)F)(=O)=O)[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([C:33]#[C:34][C:35]3[CH:45]=[CH:44][C:38]([C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:37][CH:36]=3)[CH:21]=2)[S:16]1>C1COCC1.CCCCC.[Cl-].[Cl-].[Zn+2].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:8][C:4]1[N:5]=[CH:6][C:7]([C:23]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:33]#[C:34][C:35]4[CH:45]=[CH:44][C:38]([C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:37][CH:36]=4)[CH:21]=3)[S:16][C:15]([CH3:14])([CH3:46])[CH:24]=2)=[CH:2][CH:3]=1
Reactant: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(OS(=O)(=O)C(F)(F)F)=CC(C)(C)S3)cc1
Reactant: Cc1cc(Br)ccn1
Agent: [Pd]
Agent: [Cl-]
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Solvent: CCCCC
Product: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(c2ccc(C)nc2)=CC(C)(C)S3)cc1
Temperature: 25 °C
Reaction time: 0.67 h

Procedure:
A solution of 4-bromo-2-methylpyridine (220.0 mg, 1.28 mmol) in 2.0 mL of THF was cooled to -78° C. and tert-butyllithium (164.0 mg, 2.56 mmol, 1.5 ml of a 1.7M solution in pentane) was added to give a red-orange solution. After 30 minutes a solution of ZnCl2 (348.0 mg, 2.56 mmol) in 4.0 mL THF was slowly added via cannula. The resulting solution was warmed to room temperature, stirred for 40 minutes, and transferred via cannula to a solution of ethyl 4-(2,2-dimethyl-4-trifluoromethanesulfonyloxy-(2H)thiochromen-6-yl-ethynyl)-benzoate (Compound 224, 172.0 mg, 0.35 mmol) and tetrakis(triphenylphosphine) palladium(0) (24.0 mg, 0.02 mmol) in 2.0 mL THF. This solution was heated to 50° C. for 2 hours, cooled to room temperature, and the reaction quenched by the addition of saturated aqueous NH4Cl. The solution was extracted with EtOAc and the combined organic layers were washed with H2O and saturated aqueous NaCl before being dried (MgSO4) and concentrated under reduced pressure. The title compound, 109.0 mg (72%) was isolated by column chromatography (5% EtOAc/hexanes) as a pale-yellow solid. 1H NMR (300 MHz, CDCl3) δ: 8.45 (1H, d, J=2.0 Hz), 8.00 (2H, d, J=8.5 Hz), 7.52 (2H, d, J=8.5 Hz), 7.49 (1H, dd, J=2.3, 8.1 Hz), 7.36 (2H, m), 7.20 (1H, d, J=8.1 Hz), 7.16 (1H, d, J=1.5 Hz), 5.86 (1H, s), 4.38 (2H, q, J=7.1 Hz), 2.63 (3H, s), 1.50 (6H, s), 1.40 (3H, t, J=7.1 Hz).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]=[N:7][N:8]([CH:14]([Si](C)(C)C)C)[C:9]=1[C:10]([O:12][CH3:13])=[O:11])=[O:4].[F-].[K+]>CO.C(OCC)(=O)C.CCCCCC>[CH3:1][O:2][C:3]([C:5]1[N:6]=[N:7][N:8]([CH3:14])[C:9]=1[C:10]([O:12][CH3:13])=[O:11])=[O:4]
Reactant: COC(=O)c1nnn(C(C)[Si](C)(C)C)c1C(=O)OC
Agent: [F-]
Agent: [K+]
Solvent: CCCCCC
Solvent: CO
Solvent: CCOC(C)=O
Product: COC(=O)c1nnn(C)c1C(=O)OC
Temperature: 25 °C
Reaction time: 6 h

Procedure:
To a solution of 1-trimethylsilanylethyl-1H-[1,2,3]triazole-4,5-dicarboxylic acid dimethyl ester (10 g, 36.9 mmol) in methanol (100 mL) was added potassium fluoride (11.07 g, 184.5 mmol) at RT. The reaction mixture was stirred at RT for 6 h. After solvent removal in vacuo, the crude material was diluted with water (100 mL) and extracted with ethyl acetate (2×150 mL). The combined organic layer was washed with water (2×50 mL) and brine (50 mL), dried over anhydrous Na2SO4, filtered, and evaporated in vacuo. The product was obtained after purification by flash chromatography (using silica gel and 30% ethyl acetate/hexane) as white solid (4.3 g, 21.6 mmol, 58.5%).
Reaction SMILES: ClC1C=CC(C([O:8][C@H:9]2[C@:13]([F:15])([CH3:14])[C@H:12]([N:16]3[CH:24]=[N:23][C:22]4[C:17]3=[N:18][C:19]([NH2:26])=[N:20][C:21]=4Cl)[O:11][C@@H:10]2[CH2:27][O:28]C(=O)C2C=CC(Cl)=CC=2)=O)=CC=1.[Na].[CH3:41][O-:42].Cl>CO.ClCCl>[NH2:26][C:19]1[N:18]=[C:17]2[C:22]([N:23]=[CH:24][N:16]2[C@@H:12]2[O:11][C@H:10]([CH2:27][OH:28])[C@@H:9]([OH:8])[C@:13]2([F:15])[CH3:14])=[C:21]([O:42][CH3:41])[N:20]=1
Reactant: C[C@@]1(F)[C@H](OC(=O)c2ccc(Cl)cc2)[C@@H](COC(=O)c2ccc(Cl)cc2)O[C@H]1n1cnc2c(Cl)nc(N)nc21
Reactant: C[O-]
Agent: Cl
Agent: [Na]
Solvent: CO
Solvent: ClCCl
Product: COc1nc(N)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@@]1(C)F
Temperature: 25 °C

Procedure:
To a dry 5 L three-necked round flask fitted with a mechanical stirrer and an addition funnel was loaded (2R,3R,4R,5R)-5-(2-amino-6-chloro-9H-purin-9-yl)-2-(((4-chlorobenzoyl)oxy)methyl)-4-fluoro-4-methyltetrahydrofuran-3-yl 4-chlorobenzoate (6b, 313.2 g, 526.5 mmol). The solid was suspended in anhydrous methanol (2.1 L) and cooled in an ice-water bath under an atmosphere of nitrogen. A solution of sodium 25 wt. % methoxide in methanol (361 mL, 1.58 mol) was added via an additional funnel over 20 min to give a clear solution. The reaction was allowed to warm to room temperature for 6 hours to form a turbid solution. The completion of the reaction was confirmed by LC/MS by the lack of any remaining 6-chloro deprotected nucleoside. The reaction solution was acidified with con. HCl (132 mL, 1.58 mol). After standing at room temperature (1 h), the solution was filtered to remove a white precipitate. The precipitate was washed with methanol (3×50 mL). The combined filtrate was concentrated under reduced pressure to afford a sticky solid residue. The residue was mixed with 420 mL of 2 N HCl (420 mL) and dichloromethane (1 L). The organic layer was separated and the aqueous layer was extracted with additional dichloromethane (3×500 mL). To the aqueous layer, ethyl acetate (1.4 L) was added and solid sodium carbonate (86 g) was added portion-wise to neutralize the aqueous layer to ca pH 8 (caution: foaming). After separation of the organic layer, the solid in aqueous layer was dissolved by adding more water (200 mL). The aqueous layer was extracted with ethyl acetate (3×700 mL and 400 mL). The combined organic layer was dried over sodium sulfate and concentrated under reduced pressure to a light yellow color solid that was redissolved in acetone (820 mL) at 50° C. and stirred until new solid formation initiated. The saturated solution was cooled in a freezer and product was collected by filtration. The white solid was rinsed with acetone (2×150 mL) and ethyl ether (3×80 mL) and dried (0.2 mm Hg, 50° C., 4H) to a white crystalline solid, 151.6 g (92%) of material with NMR and HPLC matching material purified by chromatography.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH2:20][OH:21])[CH2:10][CH2:9]1)=O)(C)(C)C.[ClH:22]>O1CCOCC1>[ClH:22].[NH:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH2:20][OH:21])[CH2:10][CH2:9]1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccccc2CO)CC1
Agent: Cl
Solvent: C1COCCO1
Product: OCc1ccccc1C1CCNCC1
Reaction time: 1 h

Procedure:
4-(4-(2-Hydroxymethyl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (0.13 g, 0.44 mmol) was dissolved in a solution of hydrogen chloride in dioxane (4 N, 2 mL). The mixture was stirred for 1 hour and the solvent removed by evaporation under vacuum. The solid was triturated from ether to afford the title compound as a white solid (0.08 g). LCMS m/z 192.2 [M+H]+. R.T.=0.72 min (Analytical Method 4).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[H-].[Na+].Br[CH2:11][CH2:12][Cl:13].[Na+].[Cl-]>CN(C)C=O.O>[Cl:13][CH2:12][CH2:11][O:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: Oc1cccnc1
Reactant: ClCCBr
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: ClCCOc1cccnc1
Temperature: 25 °C
Yield: 119.7 %

Procedure:
Under a nitrogen atmosphere, a solution of 3-hydroxypyridine (2.00 g, 21.0 mmol) in N,N-dimethylformamide (DMF) (10 mL) was added drop-wise over 5 min to a cold (0-5° C.), stirring slurry of sodium hydride (0.756 g of an 80% dispersion in mineral oil, 27.5 mmol) in DMF (15 mL). The mixture was allowed to stir and warm to ambient temperature over 1 h. Next, 1-bromo-2-chloroethane (3.60 g, 25.2 mmol) was added drop-wise over 5 min. The resulting dark-brown mixture was stirred at ambient temperature for 4 h. Water (30 mL) was added, followed by saturated NaCl solution (25 mL), and the mixture was extracted with ether (4×50 mL). The combined ether extracts were dried (Na2SO4), filtered, and concentrated by rotary evaporation to a residue that was dried briefly under high vacuum to give 3.96 g (66.1%) of a light-brown oil.
Reaction SMILES: [CH:1]([C@@:3]1([CH2:9][OH:10])[O:7][C:6](=[O:8])[CH2:5][CH2:4]1)=[CH2:2].[CH2:11](Br)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>CN(C=O)C.[Ag-]=O>[CH2:11]([O:10][CH2:9][C:3]1([CH:1]=[CH2:2])[O:7][C:6](=[O:8])[CH2:5][CH2:4]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: C=C[C@]1(CO)CCC(=O)O1
Reactant: BrCc1ccccc1
Agent: O=[Ag-]
Solvent: CN(C)C=O
Product: C=CC1(COCc2ccccc2)CCC(=O)O1
Yield: 80.1 %

Procedure:
A solution of 2.13 (0.140 g, 1.0 mmol) in DMF (5 mL) was stirred with silver(I) oxide (0.232 g, 1.0 mmol) and benzyl bromide (0.3 mL, 2.5 mmol) for 5 days at room temperature. The reaction mixture was filtered, diluted with water, and extracted thrice with EtOAc. The organic layer was washed with water, dried (Na2SO4), and concentrated. The residue was purified by flash column chromatography over silica gel with hexanes:EtOAc (2:1) as eluant to give the intermediate 5-[(benzyloxy)methyl]-5-vinyl-tetrahydro-2-furanone (0.186 g, 80%) as an oil; [α]22D -29.68° (c 3.08, CHCl3); IR (neat) 1772 (C=O) and 1653 cm-1 (C=C); 1H NMR (CDCl3) δ 2.05 (m, 1 H, H-4a), 2.35-2.74 (m, 3 H, H-4b, H-3), 3.55 (AB q, J=10.4 Hz, 2 H, CH2OH), 4.60 (AB q, J=12.0 Hz, 2 H, CH2OCH2Ph), 5.22 (dd, J=10.9, 0.5 Hz, 1 H, CH=CHH), 5.37 (dd, J=17.3, 0.6 Hz, 1 H, CH=CHH), 5.88 (dd, J=17.3, 10.9 Hz, 1 H, CH=CH2); 13C NMR (CDCl3) δ 28.88, 29.37, 73.66, 74.50, 86.81, 115.73, 127.58, 127.80, 128.46, 136.72, 137.65, 176.82. Anal. Calcd for C14H16O3 : C, 72.39; H, 6.94. Found: C, 72.62; H, 6.92.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:12]2[CH:17]=[C:16]([O:18][C:19]([F:24])([F:23])[CH:20]([F:22])[F:21])[CH:15]=[C:14]([F:25])[CH:13]=2)[NH:9][CH:10]=O)=[CH:4][C:3]=1[O:26][CH:27]([CH3:29])[CH3:28].CCN(CC)CC.P(Cl)(Cl)(Cl)=O>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:12]2[CH:17]=[C:16]([O:18][C:19]([F:23])([F:24])[CH:20]([F:22])[F:21])[CH:15]=[C:14]([F:25])[CH:13]=2)[N+:9]#[C-:10])=[CH:4][C:3]=1[O:26][CH:27]([CH3:29])[CH3:28]
Reactant: CC(C)Oc1cc(C(NC=O)c2cc(F)cc(OC(F)(F)C(F)F)c2)ccc1F
Solvent: C1CCOC1
Solvent: O=P(Cl)(Cl)Cl
Solvent: CCN(CC)CC
Product: [C-]#[N+]C(c1cc(F)cc(OC(F)(F)C(F)F)c1)c1ccc(F)c(OC(C)C)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 66.9 %

Procedure:
To a solution of (4-fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanamine (2.8 g, 7.1 mmol) in CH2Cl2 (30 mL) at 0° C. was added acetic formic anhydride (2.8 mL, formed by heating a 2:1 v/v ratio of acetic anhydride and formic acid at 60° C. for 2 h). The reaction mixture was allowed to warm to room temperature and stirred for 0.5 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by ISCO (120 g silica gel column, 0 to 60% EtOAc/hexane over 60 min gradient) to give N-((4-fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methyl)formamide (2.56 g, 85% yield) as a colorless oil. LCMS: RT=1.99 min [M+H] 422.0 (Phenomenex Luna C18 4.6×30 mm column, eluting with 10-90% MeOH/H2O containing 0.1% TFA, 2 min gradient, flow rate 5 mL/min, wavelength 220 nm). To a solution of N-((4-fluoro-3-isopropoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methyl)formamide (225 mg, 0.53 mmol) in THF (2 mL) at 0° C. was added Et3N (0.4 mL, 2.9 mmol) followed by phosphorous oxychloride (74 μL, 0.80 mmol). The reaction mixture was allowed to warm to room temperature and stirred for 4 h. The reaction mixture was diluted with ice water (15 mL) and extracted with Et2O (3×15 mL). The combined organic layers were washed with sat. NaCl (20 mL), dried over anhydrous MgSO4, filtered and concentrated. The residue was purified by ISCO (12 g silica gel column, 0-50% EtOAc/hexane over 30 min) to yield 1-fluoro-4-((3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)(isocyano)methyl)-2-isopropoxybenzene (143 mg, 67% yield) as a pale yellow oil. LCMS: RT=2.13 min [M−NC] 377 (Phenomenex Luna C18 4.6×30 mm column, eluting with 10-90% MeOH/H2O containing 0.% TFA, 2 min gradient, flow rate 5 mL/min, wavelength 220 nm); 1H NMR (400 MHz, CDCl3) δ ppm 7.07-7.13 (1H, m), 6.91-7.03 (4H, m), 6.84-6.86 (1H, m), 5.78-6.04 (1H, m), 5.82 (1H, s), 4.54 (1H, ddd, J=11.97, 6.15, 6.04 Hz), 1.35 (6H, t, J=5.05 Hz).
Reaction SMILES: N1C=CC=CC=1.[C:7]([O:11][C:12]([N:14]1[CH2:18][C@@H:17]([NH:19][S:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)(=[O:22])=[O:21])[CH2:16][C@H:15]1[CH2:29][OH:30])=[O:13])([CH3:10])([CH3:9])[CH3:8]>ClCCl.CCCCCC.C(OCC)(=O)C.[O-2].[O-2].[O-2].[Cr+6]>[C:7]([O:11][C:12]([N:14]1[CH2:18][C@@H:17]([NH:19][S:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)(=[O:22])=[O:21])[CH2:16][C@H:15]1[CH:29]=[O:30])=[O:13])([CH3:10])([CH3:9])[CH3:8]
Reactant: CC(C)(C)OC(=O)N1C[C@@H](NS(=O)(=O)c2ccccc2)C[C@H]1CO
Agent: [Cr+6]
Agent: [O-2]
Solvent: CCCCCC
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1C[C@@H](NS(=O)(=O)c2ccccc2)C[C@H]1C=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of pyridine (8.5 ml) in dichloromethane (150 ml) was added chromium trioxide (5.55 g) in an ice bath and the mixture was stirred at room temperature for 1 hour. To the solution were added Celite and a solution of (2S,4S)-1-t-butoxycarbonyl-2-hydroxymethyl-4-phenylsulfonylaminopyrrolidine (3.4 g) in dichloromethane (20 ml) and the mixture was stirred at room temperature for 1 hour. After being diluted with a mixture of n-hexane and ethyl acetate (1:1, 150 ml), the solution was passed through silica gel and the solvent was evaporated in vacuo to give (2S,4S)-1-t-butoxycarbonyl-2-formyl-4-phenylsulfonylaminopyrrolidine as a pale yellow oil.
Reaction SMILES: F[B-](F)(F)F.[CH3:6][O+:7]([CH3:9])C.C(N(CC)C(C)C)(C)C.[C:19]([C:21]1[N:26]=[CH:25][C:24]([CH:27]([C:42]2C(=O)[CH2:46][CH2:45][CH2:44][C:43]=2[OH:49])[NH:28][C:29]([NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[CH:33]=2)=[O:30])=[CH:23][CH:22]=1)#[N:20]>ClCCl>[C:19]([C:21]1[N:26]=[CH:25][C:24]([CH:27]([C:42]2[C:43](=[O:49])[CH2:44][CH2:45][CH2:46][C:6]=2[O:7][CH3:9])[NH:28][C:29]([NH:31][C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:39])[F:40])[CH:33]=2)=[O:30])=[CH:23][CH:22]=1)#[N:20]
Reactant: C[O+](C)C
Reactant: N#Cc1ccc(C(NC(=O)Nc2cccc(C(F)(F)F)c2)C2=C(O)CCCC2=O)cn1
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COC1=C(C(NC(=O)Nc2cccc(C(F)(F)F)c2)c2ccc(C#N)nc2)C(=O)CCC1
Temperature: 25 °C

Procedure:
Trimethyloxonium tetrafluoroborate (121 mg, 0.82 mmol) is added to a solution of N,N-diisopropylethylamine (276 μL, 1.58 mmol) and 1-((6-cyanopyridin-3-yl)(2-hydroxy-6-oxocyclohex-1-enyl)methyl)-3-(3-(trifluoromethyl)phenyl)urea (intermediate 30, 346 mg, 0.804 mmol) in dichloromethane (10 mL). The mixture is stirred at room temperature over night, and another portion of trimethyloxonium tetrafluoroborate (121 mg, 0.82 mmol) is added. After 1 h the mixture is diluted with dichloromethane, and washed with water and saturated aqueous sodium chloride solution. The organic layer is dried over Na2SO4 and concentrated under reduced pressure. Yield: 300 mg; ESI mass spectrum [M+H]+=445, Retention time HPLC: 1.09 min (V011_S01).
Reaction SMILES: C(OCC)(=O)[CH2:2][C:3](OCC)=[O:4].[Na].[O:13]1[CH2:17][CH2:16][CH:15]([CH:18]=[CH:19][C:20](=[O:22])[CH3:21])[CH2:14]1.[OH-].[Na+]>C(O)C.C(O)(C)C>[O:13]1[CH2:17][CH2:16][CH:15]([CH:18]2[CH2:2][C:3](=[O:4])[CH2:21][C:20](=[O:22])[CH2:19]2)[CH2:14]1
Reactant: CCOC(=O)CC(=O)OCC
Reactant: CC(=O)C=CC1CCOC1
Agent: [Na+]
Agent: [Na]
Agent: [OH-]
Solvent: CC(C)O
Solvent: CCO
Product: O=C1CC(=O)CC(C2CCOC2)C1
Temperature: 25 °C
Reaction time: 0.42 h

Procedure:
Diethyl malonate (6.50 ml, 43 mmol) is added dropwise to a cooled (ice-bath) solution of sodium (1.07 g, 46 mmol) in anhydrous ethanol (60 ml) and once the addition is complete the cooling bath is removed and the reaction mixture is stirred at room temperature for 25 minutes. The mixture is cooled in an ice bath and a solution of 4-(tetrahydrofuran-3-yl)-3-buten-2-one (5.0 g, 36 mmol) in ethanol (30 ml) is added dropwise. Once the addition is complete the cooling bath is removed and the reaction mixture is stirred at room temperature for 19 hours. The reaction mixture is acidified to pH 3 by dropwise addition of 2M aqueous hydrochloric acid, water added to dissolve any precipitate formed and the reaction mixture is extracted into dichloromethane. The organic extracts are dried over anhydrous magnesium sulphate, filtered and the filtrate is concentrated in vacuo to afford a yellow oil which is taken up in isopropanol (35 ml) and a 2M aqueous solution of sodium hydroxide (100 ml) is added. The reaction mixture is stirred at room temperature for 20 hours. The reaction mixture is concentrated in vacuo to remove isopropanol then heated to 70° C. A solution of 2M aqueous hydrochloric acid is added carefully until the reaction mixture reached pH 1. The reaction mixture is heated for 1½ hours at 70° C., then cooled to room temperature, diluted with water and the product is extracted into ethyl acetate. The organic extracts are combined, dried over anhydrous magnesium sulphate, filtered and the filtrate is concentrated in vacuo to give 5-(tetrahydrofuran-3-yl)cyclohexane-1,3-dione as a yellow solid.
Reaction SMILES: [C:1]([OH:4])(=[S:3])[CH3:2].[C:5]([O-:8])(=[S:7])[CH3:6].[Fe+2:9].[C:10]([O-:13])(=[S:12])[CH3:11].[Fe]=S.S>O>[C:1]([O-:4])(=[S:3])[CH3:2].[Fe+3:9].[C:5]([O-:8])(=[S:7])[CH3:6].[C:10]([O-:13])(=[S:12])[CH3:11]
Reactant: [Fe+2]
Reactant: CC(O)=S
Agent: S=[Fe]
Agent: CC([O-])=S
Agent: S
Solvent: O
Product: [Fe+3]

Procedure:
In the reactions above, a major portion, up to about 99% of the iron oxides remain unreacted. When ferrous oxide is completely reacted with thioacetic acid, the reaction product is dark green iron (II) thioacetate, a compound that is stable at room temperature. Heating the solid or boiling with water causes rapid decomposition yielding a variety of products including iron sulfide and hydrogen sulfide. The corresponding reaction with ferric oxide is quite complex as shown above, yielding iron (III) thioacetate. Iron (III) thioacetate is not stable at room temperature and hydrolyzes slowly, eventually yielding iron acetate, iron sulfide and sulfur. For the sulfur containing thiolic acids, the electrode activator it is believed comprises a mixture of the iron thio-salt and iron sulfide.
Reaction SMILES: [CH3:1][S:2][C:3]1[N:10]2[C:6]([S:7][C:8]([C:11]3[C@H:12]([CH3:35])[C@@H:13]4[C@@H:30]([C@H:31]([OH:33])[CH3:32])[C:29](=[O:34])[N:14]4[C:15]=3[C:16]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=3)=[O:17])=[CH:9]2)=[C:5]([S:36][CH3:37])[N:4]=1.IC[C:40]([NH2:42])=[O:41]>CC(C)=O>[C:40]([CH2:37][S:36][C:5]1[N:4]=[C:3]([S:2][CH3:1])[N:10]2[CH:9]=[C:8]([C:11]3[C@H:12]([CH3:35])[C@@H:13]4[C@@H:30]([C@H:31]([OH:33])[CH3:32])[C:29](=[O:34])[N:14]4[C:15]=3[C:16]([O:18][CH2:19][C:20]3[CH:21]=[CH:22][C:23]([N+:26]([O-:28])=[O:27])=[CH:24][CH:25]=3)=[O:17])[S:7][C:6]=12)(=[O:41])[NH2:42]
Reactant: NC(=O)CI
Reactant: CSc1nc(SC)n2cc(C3=C(C(=O)OCc4ccc([N+](=O)[O-])cc4)N4C(=O)[C@H]([C@@H](C)O)[C@H]4[C@H]3C)sc12
Solvent: CC(C)=O
Product: CSc1nc(SCC(N)=O)c2sc(C3=C(C(=O)OCc4ccc([N+](=O)[O-])cc4)N4C(=O)[C@H]([C@@H](C)O)[C@H]4[C@H]3C)cn12
Temperature: 25 °C
Reaction time: 336 h

Procedure:
4-Nitrobenzyl (1S,5R,6S)-2-[5,7-bis(methylthio)imidazo[5,1-b]thiazol-2-yl]-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate (107 mg) was dissolved in 2 ml of acetone. 2-Iodoacetamide (353 mg) was added to the solution. The mixture was stirred at room temperature for 14 days. The solvent was removed by distillation under the reduced pressure. The residue was purified by column chromatography on Sephadex LH-20 (chloroform:methanol=1:1) to prepare 88 mg of 4-nitrobenzyl (1S,5R,6S)-2-(7-carbamoylmethylthio-5-methylthioimidazo[5,1-b]thiazol-2-yl)-6-((1R)-1-hydroxyethyl)-1-methyl-1-carbapen-2-em-3-carboxylate as a crude product.