Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br.[CH3:2][N:3]1[CH2:8][CH2:7][C:6](=O)[CH2:5][CH2:4]1.BrBr.[CH3:12][O:13][C:14]1[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[C:16]([O:22][CH3:23])[CH:15]=1.[OH-:24].[Na+]>C(O)(=O)C.O>[OH:24][CH:5]1[C:6]([C:15]2[C:16]([O:22][CH3:23])=[CH:17][C:18]([O:20][CH3:21])=[CH:19][C:14]=2[O:13][CH3:12])=[CH:7][CH2:8][N:3]([CH3:2])[CH2:4]1
Reactant: [OH-]
Reactant: CN1CCC(=O)CC1
Reactant: COc1cc(OC)cc(OC)c1
Agent: Br
Agent: BrBr
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: COc1cc(OC)c(C2=CCN(C)CC2O)c(OC)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
75.7 ml (0.44 mol) of 33% strength HBr in glacial acetic acid were added to 100 ml of glacial acetic acid and 50 g (0.44 mol) of 1-methylpiperidin-4-one (III) were then vigorously added dropwise at 20-25° C. with ice-cooling. 70.4 g (0.44 mol) of bromine were added dropwise at 20-25° C. under nitrogen in the course of 30 min to the suspension of the hydrobromide obtained in this way, a clear, yellowish solution being obtained. This was stirred at 25° C. for a further 60 min and 67.2 g (0.40 mol) of 1,3,5-trimethoxybenzene (V) were then added to the reaction solution. It was then stirred at 25° C. for 1 h. After this, 400 ml of water were allowed to run in and the mixture was heated to reflux for 3 h. The reaction mixture was allowed to stand at room temperature overnight, diluted with 400 ml of water and then cooled to 10° C., and a total of 320 ml of conc. sodium hydroxide solution were added dropwise at this temperature in the course of 4 h to the well stirred mixture (pH after addition 10.7). In the course of this the allyl alcohol (VII) first precipitated in slightly oily form, but then on longer stirring became solid and could readily be filtered off with suction. The dark yellow precipitate was filtered off with suction, washed with water and dried well. The crude product was then stirred with 80 ml of acetone, filtered off with suction and dried in vacuo.
Reaction SMILES: II.Br[C:4]([CH3:10])([CH3:9])[C:5]([O:7][CH3:8])=[O:6].[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][C:20](OC)=[O:21])=[CH:15][CH:14]=1.S(=O)(=O)(O)O>O1CCCC1.[Zn]>[CH3:9][C:4]([CH3:10])([C:20]([CH2:19][C:16]1[CH:17]=[CH:18][C:13]([O:12][CH3:11])=[CH:14][CH:15]=1)=[O:21])[C:5]([O:7][CH3:8])=[O:6]
Reactant: COC(=O)C(C)(C)Br
Reactant: COC(=O)Cc1ccc(OC)cc1
Agent: II
Agent: O=S(=O)(O)O
Agent: [Zn]
Solvent: C1CCOC1
Product: COC(=O)C(C)(C)C(=O)Cc1ccc(OC)cc1
Reaction time: 5 h
Yield: 60 %

Procedure:
To a gently refluxing suspension of 227 g of granulated zinc, activated by the addition of 1 g of iodine, in 500 ml of dry tetrahydrofurane there is dropped with mechanical stirring and under exclusion of moisture, a solution of 700 g of methyl 2-bromoisobutyrate and 540 g of methyl p-methoxy-phenylacetate in 500 ml of tetrahydrofurane. As soon as the reaction has started, apparent from the formation of a turbidity and stronger reflux, the addition is continued at such a rate as to maintain gentle reflux with minimal application of external heating. After all of the solution has been added, stirring and refluxing is continued for 5 hours. Then the reaction mixture is cooled with ice and 1500 ml of 4 N sulphuric acid is added dropwise with vigorous stirring. The organic layer is separated, after the eventual removal of some solid material by filtration, and the aqueous solution extracted with ether. The combined organic solutions are washed with an aqueous solution of sodium bicarbonate. Evaporation of the solvent leaves the crude ester which is purified by distillation in vacuo. Yield 60 - 65%, boiling point 145° C (1 mm), nD20 1.5140.
Reaction SMILES: C12(C[O:12]C3C=CC(C#N)=CC=3C3C(OC)=NC=CC=3)CC3CC(CC(C3)C1)C2.[C:29]12([CH2:39][O:40][C:41]3[CH:48]=[CH:47][C:44]([C:45]#[N:46])=[CH:43][C:42]=3[Br:49])[CH2:38][CH:33]3[CH2:34][CH:35]([CH2:37][CH:31]([CH2:32]3)[CH2:30]1)[CH2:36]2>>[C:29]12([CH2:39][O:40][C:41]3[CH:48]=[CH:47][C:44]([C:45]([NH2:46])=[O:12])=[CH:43][C:42]=3[Br:49])[CH2:30][CH:31]3[CH2:37][CH:35]([CH2:34][CH:33]([CH2:32]3)[CH2:38]1)[CH2:36]2
Reactant: COc1ncccc1-c1cc(C#N)ccc1OCC12CC3CC(CC(C3)C1)C2
Reactant: N#Cc1ccc(OCC23CC4CC(CC(C4)C2)C3)c(Br)c1
Product: NC(=O)c1ccc(OCC23CC4CC(CC(C4)C2)C3)c(Br)c1

Procedure:
Following the procedure as described in Example 38 step 3 and making variations as required to replace 4-(adamantan-1-ylmethoxy)-3-(2-methoxypyridin-3-yl)benzonitrile with 4-(adamantan-1-ylmethoxy)-3-bromobenzonitrile, the title compound was obtained as a colorless solid (1.80 g, 98%): 1H NMR (300 MHz, CDCl3) δ 7.99-7.97 (m, 1H), 7.74-7.69 (m, 1H), 6.87-6.83 (m, 1H), 5.86 (br s, 2H), 3.57 (s, 2H), 2.02 (br s, 3H), 1.79-1.58 (m, 12H); MS (ES+) m/z: 364.1, 366.1 (M+1).
Reaction SMILES: [C:1]([C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][NH:9][CH2:10]2)=[CH:5][CH:4]=1)#[N:2].C([O-])([O-])=O.[K+].[K+].Br[CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22]>CC#N>[C:1]([C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][N:9]([CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:10]2)=[CH:5][CH:4]=1)#[N:2]
Reactant: CC(C)(C)OC(=O)CBr
Reactant: N#Cc1ccc2c(c1)CNCC2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CC(C)(C)OC(=O)CN1CCc2ccc(C#N)cc2C1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a suspension of 7-cyano-1,2,3,4-tetrahydroisoquinoline (ABCR, 2 g; 12.64 mmol) and K2CO3 (3.49 g, 25.28 mmol) in CH3CN (40 mL), was added tert-butyl bromoacetate (1.96 mL; 13.27 mmol) and the reaction mixture was stirred at RT for 4 hours. Solvents were removed under vacuum and solid residue was extracted with EtOAc from a saturated aqueous solution of NaHCO3, dried over MgSO4 and evaporated under vacuum to give the title compound a as colorless oil (3.32 g; 96%). 1H NMR (DMSO-d6) δ 7.55 (m, 2H), 7.30 (m, 1H), 3.72 (s, 2H), 3.31 (s, 2H), 2.86-2.79 (m, 4H), 1.49 (s, 9H). LC/MS (Method B): 217.1 (M+1-1)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[N:12]=[CH:11][N:10](/[CH:13]=[CH:14]\[C:15]([NH:17][NH2:18])=[O:16])[N:9]=2)[CH:5]=[C:4]([O:19][CH3:20])[N:3]=1.[CH:21](OC)(OC)OC.CS(O)(=O)=O.CCOC(C)=O.CCCCCC>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[N:12]=[CH:11][N:10](/[CH:13]=[CH:14]\[C:15]3[O:16][CH:21]=[N:18][N:17]=3)[N:9]=2)[CH:5]=[C:4]([O:19][CH3:20])[N:3]=1
Reactant: COc1cc(-c2ncn(/C=C\C(=O)NN)n2)cc(Cl)n1
Reactant: COC(OC)OC
Agent: CS(=O)(=O)O
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COc1cc(-c2ncn(/C=C\c3nnco3)n2)cc(Cl)n1

Procedure:
In a 100-mL, 3N round-bottomed flask equipped with Thermometer pocket fitted with nitrogen inlet, condenser and a rubber septum, (Z)-3-(3-(2-chloro-6-methoxypyridin-4-yl)-1H-1,2,4-triazol-1-yl)acrylohydrazide (0.7 g, 1.0 eq.), trimethyl orthoformate (0.3 mL, 1.1 eq.) and methane sulfonic acid (0.07 mL, 0.5 eq) was dissolved in THF (70 mL) resulting reaction mixture was stir at reflux temperature. The progress of the reaction was followed by TLC analysis on silica gel with 80% EtOAc-hexane as mobile phase which shows that starting material was consumed after 3 h. Reaction was quenched by water, solid material was observed that was filter on Buchner funnel to give crude material (0.490 g). The crude material was subjected to combiflash purification using ethyl acetate:hexane as mobile phase; Yield: 0.03 g (4.14%); (Z)-2-(2-(3-(2-chloro-6-methoxypyridine-4-yl)-1H-1,2,4-triazol-1-yl)vinyl)-1,3,4-oxadiazole: 1H NMR: (400 MHz, DMSO) δ=9.45 (s, 1H), 9.36 (s, 1H), 7.737-7.762 (d, J=10 Hz, 1H), 7.48 (s, 1H), 7.24 (s, 1H), 6.719-6.745 (d, J=10.4 Hz, 1H), 3.92 (s, 3H). LC-MS: Calculated for C12H9ClN6O2 (M+H)+ 304.69 Found: 304.81 Retention time: 3.354 min (100%).
Reaction SMILES: [C:1]([NH:4][C@H:5]([C:14]([NH:16][C@H:17]([C:21]([OH:23])=O)[CH:18]([CH3:20])[CH3:19])=[O:15])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)(=[O:3])[CH3:2].[NH:24]1[CH2:46][CH2:45][CH2:44][CH2:43][CH:25]1[C:26]([NH:28][CH:29]1[CH:33]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[O:32][C:31](=[O:42])[CH2:30]1)=[O:27].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.C(OCC)(=O)C.ClCCl>[C:1]([NH:4][C@H:5]([C:14]([NH:16][C@H:17]([C:21]([N:24]1[CH2:46][CH2:45][CH2:44][CH2:43][CH:25]1[C:26]([NH:28][CH:29]1[CH:33]([O:34][CH2:35][C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[O:32][C:31](=[O:42])[CH2:30]1)=[O:27])=[O:23])[CH:18]([CH3:19])[CH3:20])=[O:15])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([OH:13])=[CH:11][CH:12]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@H](C(=O)O)C(C)C
Reactant: O=C1CC(NC(=O)C2CCCCN2)C(OCc2ccccc2)O1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CC(=O)N[C@@H](Cc1ccc(O)cc1)C(=O)N[C@H](C(=O)N1CCCCC1C(=O)NC1CC(=O)OC1OCc1ccccc1)C(C)C
Reaction time: 18 h
Yield: 45.7 %

Procedure:
N-Acetyl-tyrosinyl-valine (464 mg, 1.44 mmol) and N-Pipecolyl-4-amino-5-benzyloxy-2-oxotetrahydrofuran (412 mg, 1.3 mmol) were dissolved in 5 ml each of dimethylformamide and dichloromethane and cooled to 0° C. To the cooled solution was added 1-hydroxybenzotriazole (HOBT; 210 mg, 1.56 mmol) followed by the addition of 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide hydrochloride (EDC; 326 mg, 1.7 mmol). After stirring for 18 hours, the mixture was diluted with ethyl acetate and washed with water, 10% sodium hydrogen sulfate, 10% sodium bicarbonate, and water. The organic layer was concentrated to give a crude solid that was purified by flash chromatography (SiO2) eluting with 94:6:1 (dichloromethane:isopropanol:pyridine) to give 370 mg of the title compound.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([C:15](O)=O)=[CH:11][C:10]=1[CH2:18][O:19][CH3:20])[CH3:2].[NH2:21][C:22](=[N:41][OH:42])[C:23]1[CH:32]=[C:31]2[C:26]([CH2:27][CH2:28][N:29]([CH2:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30]2)=[CH:25][CH:24]=1>CCOC(C)=O>[CH2:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:42][N:41]=[C:22]([C:23]3[CH:32]=[C:31]4[C:26]([CH2:27][CH2:28][N:29]([CH2:33][C:34]([O:36][C:37]([CH3:38])([CH3:39])[CH3:40])=[O:35])[CH2:30]4)=[CH:25][CH:24]=3)[N:21]=2)=[CH:11][C:10]=1[CH2:18][O:19][CH3:20])[CH3:2]
Reactant: CCc1ccccc1-c1ccc(C(=O)O)cc1COC
Reactant: CC(C)(C)OC(=O)CN1CCc2ccc(C(N)=NO)cc2C1
Solvent: CCOC(C)=O
Product: CCc1ccccc1-c1ccc(-c2nc(-c3ccc4c(c3)CN(CC(=O)OC(C)(C)C)CC4)no2)cc1COC

Procedure:
Title compound was prepared following general procedure 2 starting from Intermediate 23 (162 mg; 0.6 mmol) and Intermediate 5 (174 mg; 0.6 mmol). The reaction mixture was diluted with EtOAc, washed with water and brine and evaporated under vacuum. Purification by silica column chromatography (c-Hex/(DCM/EtOAc 1:1), 90/10 to 50/50) afforded the title compound as a yellowish oil. LC/MS (method B): 541.4 (M+H)+. HPLC (Method A) Rt 4.90 min (Purity: 96.1%).
Reaction SMILES: [CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]=[CH:9][C:10]([OH:12])=[O:11])=[CH:4][CH:3]=1.S(=O)(=O)(O)O.[CH2:18](O)[CH3:19]>>[CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]=[CH:9][C:10]([O:12][CH2:18][CH3:19])=[O:11])=[CH:4][CH:3]=1
Reactant: CCO
Reactant: Cc1ccc(C=CC(=O)O)cn1
Agent: O=S(=O)(O)O
Product: CCOC(=O)C=Cc1ccc(C)nc1

Procedure:
A stirred mixture of 3-(6-methyl-3-pyridyl)acrylic acid (50.70 g), dry ethanol (350 ml) and concentrated sulphuric acid (25 ml) was heated under reflux for 18 hours and ethanol (~250 ml) was removed by evaporation. The residue was poured into ice-aqueous ammonia and the mixture was extracted with ether. The ether extracts were washed with water and evaporated to an oil which crystallised on standing to give ethyl 3-(6-methyl-3-pyridyl)acrylate m.p. 36°-37°.
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]=[C:5]([OH:13])[C:6]2[S:12][CH2:11][CH2:10][CH2:9][C:7]=2[N:8]=1.[C-:14]#[N:15].[Na+].O>CS(C)=O>[C:14]([CH2:2][C:3]1[N:4]=[C:5]([OH:13])[C:6]2[S:12][CH2:11][CH2:10][CH2:9][C:7]=2[N:8]=1)#[N:15]
Reactant: [C-]#N
Reactant: Oc1nc(CCl)nc2c1SCCC2
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: N#CCc1nc(O)c2c(n1)CCCS2
Temperature: 25 °C
Reaction time: 3.5 h

Procedure:
Product from Example 3, step A, (1.8 g, 0.01 mol) was dissolved in 10 ml of DMSO and sodium cyanide (1.0 g) was added. The reaction mixture was stirred at 25° C. for 3.5 hours and then poured into water (150 ml). The solution was extracted with ethyl acetate, the ethyl acetate was dried and then evaporated to give the title compound as an oil that was used directly in Step B hereof.
Reaction SMILES: [C:1]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][OH:14])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:15]1([CH3:25])[CH:20]=[CH:19][C:18](S(O)(=O)=O)=[CH:17][CH:16]=1.[CH:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>>[C:1]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][CH:1]([O:9][CH2:10][CH3:11])[C:2]#[C:26][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:15][CH3:25])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(OCCCCO)c1ccccc1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: c1ccccc1
Product: CCCCCCCCCCCCC#CC(OCC)OCCCCOC(=O)c1ccccc1
Temperature: 25 °C

Procedure:
32 g of ethane-2,2'-[2-pentadecyn-1-ylidene bis(oxy)]bis, 25 g of 4-benzoyloxy-1-butanol, and 100 mg of p-toluene sulfonic acid were refluxed in a dry apparatus in 300 ml of benzene using a Dean-Stark trap. After evaporating 75 ml of solvent, the solution was cooled to room temperature diluted with CHCl3, washed with saturated aqueous NaHCO3, then with water and dried over Na2SO4. The resulting oil (13 g) after evaporation of the solvent was purified by column chromatography (SiO2) (CHCl3). The partially purified compound was rechromatographed (SiO2) (50% Hexanes/CHCl3). Yield: 1.5 g.
Reaction SMILES: O1CCCC1.C(CC[N:10]1[C:14]([N+:15]([O-:17])=[O:16])=[CH:13][N:12]=[C:11]1[S:18][C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][CH:20]=1)#N.Cl.O>C(OCC)(=O)C>[N+:15]([C:14]1[N:10]=[C:11]([S:18][C:19]2[CH:20]=[CH:21][C:22]([N+:25]([O-:27])=[O:26])=[CH:23][CH:24]=2)[NH:12][CH:13]=1)([O-:17])=[O:16]
Reactant: N#CCCn1c([N+](=O)[O-])cnc1Sc1ccc([N+](=O)[O-])cc1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: O=[N+]([O-])c1ccc(Sc2nc([N+](=O)[O-])c[nH]2)cc1
Reaction time: 5 h
Yield: 89.9 %

Procedure:
To tetrahydrofuran (1 ml) solution of 1-(2-cyanoethyl)-5-nitro-2-(4-nitrophenylthio)imidazole (36 mg) was added 1,8-diazabicyclo[5.4.0]undecene-7 (0.02 ml) at a room temperature, and stirred at the same temperature for 5 hours. To the reaction mixture were added 1N hydrochloric acid (0.2 ml), water and ethyl acetate, then the organic layer was taken by liquid separation. The ethyl acetate layer was washed with water and an aqueous solution being saturated with sodium chloride, then dried over anhydrous sodium sulfate. The residue obtained by removal of the solvent by distillation was purified by use of a silica gel column chromatography (eluent: dichloromethane/ethyl acetate=4/1), there was obtained 4-nitro-2-(4-nitrophenylthio)imidazole (27 mg, yield 91%) as pale yellow powder product.
Reaction SMILES: FC(F)(F)C(O)=O.C[O:9][C:10](=[O:40])[C@H:11]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH2:28][CH2:29][C:30]2[CH:39]=[CH:38][C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH:31]=2)[CH:22]=1)[NH:12]C(OC(C)(C)C)=O.O.[OH-].[Li+].Cl>C(Cl)Cl.O>[CH:31]1[C:32]2[C:37](=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:38]=[CH:39][C:30]=1[CH2:29][CH2:28][O:27][C:23]1[CH:22]=[C:21]([CH:26]=[CH:25][CH:24]=1)[CH2:20][C@@H:11]([C:10]([OH:40])=[O:9])[NH2:12]
Reactant: COC(=O)[C@H](Cc1cccc(OCCc2ccc3ccccc3c2)c1)NC(=O)OC(C)(C)C
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: N[C@@H](Cc1cccc(OCCc2ccc3ccccc3c2)c1)C(=O)O
Reaction time: 0.5 h
Yield: 59 %

Procedure:
Trifluoroacetic acid (3 ml) was added to a solution of N-t-butoxycarbonyl-3-[2-(2-naphthyl)ethoxy]-L-phenylalanine methyl ester (125 mg, 0.278 mmol) in methylene chloride (3 ml) under ice cooling and the mixture was stirred at the same temperature for 30 min. The solvent of the reaction mixture was distilled off at room temperature under reduced pressure. The residue was triturated with n-hexane and collected by filtration. The resultant solid was dissolved in tetrahydrofuran (1.2 ml)-water (0.6 ml). Lithium hydroxide mono-hydrate (41 mg, 0.973 mmol) was added to the solution with stirring under ice cooling and the mixture was reacted at the same temperature for 12 hrs. The reaction mixture was diluted with water (2 ml) and adjusted to pH 3-4 with 1N HCl. After the addition of water (25 ml), the mixture was stirred at room temperature for 1 hr. The precipitates were collected by filtration, washed with water and then dried under reduced pressure to give 3-[2-(2-naphthyl)ethoxy]-L-phenylalanine (55 mg, 59%) as colorless crystals.
Reaction SMILES: [C:1]([OH:6])(=[O:5])[C:2]([OH:4])=[O:3].[Gd:7]>[Ga]>[C:1]([O-:6])(=[O:5])[C:2]([O-:4])=[O:3].[Gd+3:7].[C:1]([O-:6])(=[O:5])[C:2]([O-:4])=[O:3].[C:1]([O-:6])(=[O:5])[C:2]([O-:4])=[O:3].[Gd+3:7]
Reactant: [Gd]
Reactant: O=C(O)C(=O)O
Agent: [Ga]
Product: O=C([O-])C(=O)[O-]
Product: [Gd+3]
Temperature: 80 °C

Procedure:
After pretreatment and dissolution in mineral acid of the gadolinium and gallium by-products as described above, the filtrate is heated to 80° C. and solid oxalic acid is added to precipitate gadolinium oxalate, Gd2 (C2O4)3. The precipitate, which forms immediately, is separated from gallium and transition metal impurities by conventional methods, by either vacuum filtration or centrifugation. The cake of gadolinium oxalate, thus obtained, may be slurried in a water solution containing 2% by weight of oxalic acid to remove trace adhering gallium solution. The yield of gadolinium oxalate is of the order of >95%. Direct pyrolysis of this oxalate at 850°-950° C. results in its conversion to gadolinium oxide, Gd2O3, in >95% yield and >99.99% purity.
Reaction SMILES: [CH3:1][CH:2]([CH2:6][CH2:7]/[CH:8]=[C:9](\[CH3:16])/[CH2:10][CH2:11][CH:12]=[C:13]([CH3:15])[CH3:14])[CH2:3][C:4]#N.[OH-:17].[K+].C(O)C([OH:22])C.Cl>O>[CH3:1][CH:2]([CH2:6][CH2:7]/[CH:8]=[C:9](\[CH3:16])/[CH2:10][CH2:11][CH:12]=[C:13]([CH3:15])[CH3:14])[CH2:3][C:4]([OH:22])=[O:17]
Reactant: CC(C)=CCC/C(C)=C/CCC(C)CC#N
Reactant: CC(O)CO
Reactant: [OH-]
Agent: Cl
Agent: [K+]
Solvent: O
Product: CC(C)=CCC/C(C)=C/CCC(C)CC(=O)O

Procedure:
To 40 g. of the product obtained in the above (b) step, there were added 35 g. of potassium hydroxide, 15 ml. of water and 80 ml. of propylene glycol, and the mixture was stirred at 130° C. for 7 hours. The reaction mixture was then made acidic by addition of hydrochloric acid, and was then extracted with n-hexane. The extract was washed with water and dried, and the solvent was removed by evaporation. The residue was purified by silica gel column chromatography to obtain 36 g. of the desired oily product.
Reaction SMILES: [CH2:1]([C:9]1[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[S-:16][C:17]#[N:18].[K+].BrBr.O>C(O)(=O)C>[NH2:18][C:17]1[S:16][C:14]2[CH:15]=[C:9]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH:10]=[CH:11][C:12]=2[N:13]=1
Reactant: CCCCCCCCc1ccc(N)cc1
Reactant: N#C[S-]
Agent: BrBr
Agent: [K+]
Solvent: CC(=O)O
Solvent: O
Product: CCCCCCCCc1ccc2nc(N)sc2c1
Yield: 64.5 %

Procedure:
In a 2 liters-reaction vessel, 50.0 g (0.24M) of p-octylaniline, 47.3 g (0.49M) of potassium thiocyanate and 350 ml of acetic acid were placed and cooled below 10° C. Under intersive stirring, a solution of 39.0 g of bromine in 120 ml of acetic acid was added dropwise to the above mixture in 75 minutes below 10° C., followed by reaction for 2 hours below 10° C. After the reaction, 500 ml of water was added to the reaction mixture and heated to dissolve the precipitate, followed by filtration under heating. Ammonia water was added to the filtrate so as to provide a basic solution, followed by cooling on an iced bath to precipitate a crystal. The crystal was recovered by filtration, followed by washing with water and drying to obtain a crude product. The crude product was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate) to obtain 41.2 g of 2-amino-6-octylbenzothiazole (Yield: 68%).
Reaction SMILES: C=O.[C:3](=O)([O-])O.[Na+].[Br-].[O:9]([CH2:16][C:17]([NH:19][C@@H:20]1[C:55](=[O:56])[N:22]2[C:23]([C:47]([O:49][CH2:50][C:51]([Cl:54])([Cl:53])[Cl:52])=[O:48])=[C:24]([CH2:27][P+](C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[CH2:25][S:26][C@H:21]12)=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C(Cl)Cl>[O:9]([CH2:16][C:17]([NH:19][C@@H:20]1[C:55](=[O:56])[N:22]2[C:23]([C:47]([O:49][CH2:50][C:51]([Cl:53])([Cl:52])[Cl:54])=[O:48])=[C:24]([CH:27]=[CH2:3])[CH2:25][S:26][C@H:21]12)=[O:18])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=C(COc1ccccc1)N[C@@H]1C(=O)N2C(C(=O)OCC(Cl)(Cl)Cl)=C(C[P+](c3ccccc3)(c3ccccc3)c3ccccc3)CS[C@H]12
Reactant: O=C([O-])O
Agent: C=O
Agent: [Br-]
Agent: [Na+]
Solvent: ClCCl
Product: C=CC1=C(C(=O)OCC(Cl)(Cl)Cl)N2C(=O)[C@@H](NC(=O)COc3ccccc3)[C@H]2SC1
Reaction time: 2 h
Yield: 17 %

Procedure:
40%-Aqueous formaldehyde (24 ml.) and 3%-sodium hydrogen carbonate solution (80 ml.) were added to a solution of [7β-phenoxyacetamido-4-(2,2,2-trichloroethoxycarbonyl) ceph-3-em-3-ylmethyl]-triphenylphosphonium bromide (4.93 g, 6 mmole) in methylene chloride (40 ml.). The two-phase mixture was stirred vigorously for 2 hours and the organic phase was washed with water (100 ml.), dried (MgSO4), and evaporated to an orange foam. This foam was chromatographed on Kieselgel G (Merck; 150 g) with methylene chloride and 0.5%-acetone in methylene chloride as eluants. The appropriate fractions were combined and evaporated to a colourless oil which crystallised on addition of ether. The solvent was removed to give the title ester as a white solid (0.50 g, 17%), m.p. 136° to 140° (decomp), [α]D23 - 33° (c 1.01; Me2SO), λmax. (EtOH), 296 nm (ε 12,100), νmax. (Nujol) 3300 (NH), 1764 (azetidin-2-one), 1716 (CO2R), 1668 and 1509 (CONH) and 920 cm-1 (=CH2), τ (Me2SO-d6) 0.81 (1H, d, J 8 Hz; NH), 2.67 and 2.99 (2H and 3H, 2m; C6H5O), 3.01 (1H, dd, J 11 and 18 Hz; CH=CH2), 4.19 (1H, dd, J 8 and 5 Hz; C7 -H), 4.24 (1H, d, J 18 Hz) and 4.55 (1H, d, 11 Hz) (CH=CH2), 4.71 (1H, d, J 5 Hz; C6 -H), 4.79 and 5.01 (2H, AB-q, J 12 Hz; CH2CCl3), 5.36 (2H, s; C6H5OCH2), 5.98 and 6.34 (2H, AB-q, J 18 Hz; C2 -H2).