Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:8][C:9]1[CH:40]=[CH:39][C:12]([C:13]([NH:15][C:16]([CH3:38])([CH3:37])[C:17](=[O:36])[N:18]2[CH2:23][CH2:22][N:21]([C:24](=[O:35])[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:31]([F:34])([F:33])[F:32])[CH2:20][CH2:19]2)=[O:14])=[CH:11][CH:10]=1)C1C=CC=CC=1.CO>[Pd].C(OCC)(=O)C>[CH3:38][C:16]([NH:15][C:13](=[O:14])[C:12]1[CH:11]=[CH:10][C:9]([OH:8])=[CH:40][CH:39]=1)([CH3:37])[C:17](=[O:36])[N:18]1[CH2:19][CH2:20][N:21]([C:24](=[O:35])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:31]([F:32])([F:34])[F:33])[CH2:22][CH2:23]1
Reactant: CC(C)(NC(=O)c1ccc(OCc2ccccc2)cc1)C(=O)N1CCN(C(=O)c2ccccc2C(F)(F)F)CC1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CO
Product: CC(C)(NC(=O)c1ccc(O)cc1)C(=O)N1CCN(C(=O)c2ccccc2C(F)(F)F)CC1
Reaction time: 2 h
Yield: 89.9 %

Procedure:
Pd/c (20 mg) was added to a stirred solution of 4-benzyloxy-N-{1,1-dimethyl-2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-benzamide (70 mg, 0.12 mmol) in a mixture methanol (2 mL) and ethyl acetate (5 ml) and stirring was continued at room temperature under hydrogen atmosphere for 2 hrs. The mixture was filtered over a bed of celite. The celite was washed with methanol and the filtrate was concentrated under reduced pressure to afford 50 mg (86.2% yield) of N-{1,1-dimethyl-2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-4-hydroxy-benzamide. LCMS Purity: 95.26%. 1H NMR (DMSO): δ 8.2-8.3 (bs, 1H), 7.5-7.9 (m, 6H), 7.4 (d, 2H), 6.8 (d, 2H), 3.5 (m, 6H), 3 (m, 2H), 1.4 (s, 6H).
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:11])=[C:4]([C:7]([OH:10])=[CH:8][CH:9]=1)[CH:5]=O.C(=O)([O-])[O-].[K+].[K+].[F:18][C:19]([F:28])([F:27])/[CH:20]=[CH:21]/[C:22]([O:24][CH2:25][CH3:26])=[O:23].Cl>CN(C=O)C>[Cl:1][C:2]1[C:3]([F:11])=[C:4]2[C:7](=[CH:8][CH:9]=1)[O:10][CH:20]([C:19]([F:18])([F:28])[F:27])[C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:5]2
Reactant: CCOC(=O)/C=C/C(F)(F)F
Reactant: O=Cc1c(O)ccc(Cl)c1F
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)C1=Cc2c(ccc(Cl)c2F)OC1C(F)(F)F
Temperature: 70 °C

Procedure:
To 1.1 g (6.7 mmole) of 3-chloro-2-fluoro-6-hydroxybenzaldehyde in 2 mL DMF was added 1.0 g (7.2 mmole) of potassium carbonate and 3A molecular sieves. The stirred mixture was heated to 70° C. and treated with 1.5 mL (1.69 g, 10.0 mmole) of ethyl 4,4,4-trifluorocrotonate. After lh the mixture was treated with an additional 1.5 mL of ethyl 4,4,4-trifluorocrotonate and allowed to react overnight. To the cooled mixture was added 1N HCl, the mixture extracted three times with methylene chloride and the combined organic fractions dried and concd. The resultant oil was dissolved in ether, washed three times with water and concd to give an oil. Chromatographic purification (silica, 5-10% EtOAc/hex) gave 0.76 g (35%) of a clear, yellow oil: 1H NMR (CDCl3/400 MHz) 1.37 (t, 3H, J=7.2 Hz), 4.34 (m, 2H), 5.72 (q, 1H, J=6.8 Hz), 6.77 (d, 1H, J=8.8 Hz), 7.32 (t, 1H, J=8.5 Hz), 7.92 (s, 1H); 19F NMR (CDCl3/400 MHz) −78.7 (d, 3F, J=6.8 Hz), −119.6 (d, 1F, J=7.7 Hz); 13C NMR (CDCl3/100 MHz) 14.2, 61.9, 70.8 (q, J=33.4 Hz), 110.0 (d, J=18.1 Hz), 112.6 (d, J=4.0 Hz), 114.4 (d, J=17.3 Hz), 118.2 (J=2.3 Hz), 123.2 (q, J=287.3 Hz), 129.2 (d, J=4.6 Hz), 133.2 (d, J=1.3 Hz), 152.2 (d, J=4.4 Hz), 154.9 (d, J=256.4 Hz), 163.3; MS (ESI+) 325 (M+l, 100); MS (EI) 324 (M+, 21), 255 (100), 227 (83); HRMS (EI) m/z calcd for (C13H9O3ClF4) 324.0176, found 324.0171.
Reaction SMILES: [Br:1][C:2]1[N:3]=[C:4](Br)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[CH:7]=1.[CH3:12][C:13]1[NH:17][N:16]=[C:15]([NH2:18])[CH:14]=1>CCO>[Br:1][C:2]1[N:3]=[C:4]([NH:18][C:15]2[CH:14]=[C:13]([CH3:12])[NH:17][N:16]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[CH:7]=1
Reactant: Cc1cc(N)n[nH]1
Reactant: Brc1cn2ccnc2c(Br)n1
Solvent: CCO
Product: Cc1cc(Nc2nc(Br)cn3ccnc23)n[nH]1
Temperature: 120 °C
Yield: 32.8 %

Procedure:
Example 8 was then prepared as follows. 6,8-Dibromoimidazo[1,2-a]pyrazine (278 mg, 1 mmol) and 5-methyl-1H-pyrazol-3-amine (196 mg, 2 mmol) was suspended in EtOH (2 ml). The mixture was heated with microwave at 120° C. for four hours. The mixture was then purified with HPLC to give (6-Bromo-imidazo[1,2-a]pyrazin-8-yl)-(5-methyl-1H-pyrazol-3-yl)-amine as a solid (96 mg). 1H NMR (400 MHz, DMSO) δ 8.29 (s, 1H) 7.98 (s, 1H) 7.70 (s, 1H) 6.48 (s, 1H) 2.27 (s, 3H). [M+H] calc'd for C10H9BrN6, 293; found, 293.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[NH:9][C:10](=[O:30])[CH2:11][N:12]1[CH2:17][CH2:16][N:15]([C:18](=[O:29])[CH:19](O)[CH2:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:14][CH2:13]1.C1(CCCC(O)=O)C=CC=CC=1.OC1C=CC=CC=1[C@@H](CC)C(O)=O>>[CH3:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[C:3]=1[NH:9][C:10](=[O:30])[CH2:11][N:12]1[CH2:17][CH2:16][N:15]([C:18](=[O:29])[CH2:19][CH2:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:14][CH2:13]1
Reactant: Cc1cccc(C)c1NC(=O)CN1CCN(C(=O)C(O)CCc2ccccc2)CC1
Agent: CC[C@@H](C(=O)O)c1ccccc1O
Agent: O=C(O)CCCc1ccccc1
Product: Cc1cccc(C)c1NC(=O)CN1CCN(C(=O)CCCc2ccccc2)CC1

Procedure:
Compound 13 was prepared in the manner of compound 7 substituting 4-phenylbutanoic acid for (R)-2-hydroxy-phenylbutyric acid in part C to afford compound 13: Mass spectrum (M+1) =394.40.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[OH:11]>O>[OH:11][C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:1]=1[C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[OH:11]
Reactant: Oc1ccc2ccccc2c1
Solvent: O
Product: Oc1ccc2ccccc2c1-c1c(O)ccc2ccccc12

Procedure:
2 g 2-naphthol, 11.4 g FeCl3.6H2O and 100 ml water are added to a 200 ml flask in order to perform stirring reaction in 65° C. water bath, TLC (thin layer chromatography) is adopted for tracking, the reaction product is filtered 3 hours after the reaction to obtain the solid 2,2′-dihydroxy-1,1′-binaphthyl, the 2,2′-dihydroxy-1,1′-binaphthyl is washed with 50 ml water, the washing solution is incorporated into the filtrate, 7.5 ml H2O2 with the concentration of 30% is slowly and dropwise added to the filtrate under stirring, the filtrate is continuously stirred for 10 minutes, 2 g 2-naphthol is added to perform stirring reaction at 65° C., TLC tracking is performed until the reaction comes to an end, and the reaction product is filtered to obtain the solid 2,2′-dihydroxy-1,1′-binaphthyl. The above steps are repeated so as to lead to the results in Table 6. The HPLC analysis result of the eleventh circular reaction product shows that the conversion rate of the 2-naphthol is more than 98%, and the selectivity of the 2,2′-dihydroxy-1,1′-binaphthyl is more than 99%.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([S:8]([C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-])=O)=[CH:13][CH:12]=2)(=[O:10])=[O:9])[CH:5]=[C:4]([Br:20])[N:3]=1.[NH4+].[Cl-]>CO.O1CCOCC1.O.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([S:8]([C:11]2[CH:12]=[CH:13][C:14]([NH2:17])=[CH:15][CH:16]=2)(=[O:9])=[O:10])[CH:5]=[C:4]([Br:20])[N:3]=1
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)c2cc(Br)nc(Br)c2)cc1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CO
Solvent: O
Solvent: C1COCCO1
Product: Nc1ccc(S(=O)(=O)c2cc(Br)nc(Br)c2)cc1
Yield: 81.4 %

Procedure:
22.30 g (0.052 mol) of 2,6-dibromo-4-(4-nitrobenzenesulphonyl)-pyridine were suspended in a mixture of 275 ml of methanol and 275 ml of dioxane, treated with 22.30 g of powdered iron and a solution of 22.30 g of NH4Cl in 550 ml of water and heated at reflux for 1.5 hrs. Then, the organic solvents were distilled off on a rotary evaporator and the residue was diluted with 1.0 l of dichloromethane and suction filtered. The filter material was suspended in a mixture of 250 ml of methanol and 250 ml of dichloromethane in an ultrasound bath, again suction filtered and the filtrate was retained. The first filtrate was separated in a separating funnel and the organic phase was washed with sat. sodium chloride solution, dried over MgSO4, filtered and concentrated together with the second filtrate. The residue was chromatographed on silica gel with dichloromethane. There were obtained 16.6 g (80%) of 4-(2,6-dibromopyridine-4-sulphonyl)-phenylamine as yellowish crystals; m.p.: 196-198° C. (dec.).
Reaction SMILES: [CH:1]([OH:3])=O.C(OC(=O)C)(=O)C.[CH3:11][C:12]1[CH:18]=[CH:17][CH:16]=[CH:15][C:13]=1[NH2:14]>ClCCl>[CH:1]([NH:14][C:13]1[CH:15]=[CH:16][CH:17]=[CH:18][C:12]=1[CH3:11])=[O:3]
Reactant: Cc1ccccc1N
Reactant: O=CO
Solvent: CC(=O)OC(C)=O
Solvent: ClCCl
Product: Cc1ccccc1NC=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 71.8 %

Procedure:
A mixture of formic acid (14.361 g, 0.312 mol) and acetic anhydride (12.659 g, 0.124 mol) was stirred at room temperature for 1 h under an argon atmosphere. This mixture was added to a solution of 2-methylaniline (10.710 g, 0.1 mol) in dry dichloromethane (60 ml) at such a rate that the temperature of the reaction mixture was kept between 5 and 10° C. The reaction was stirred at room temperature for 16 h and then refluxed for 4 h. The solvent was evaporated under reduced pressure, the residue was dissolved in CHCl3 (200 mL) and washed with a saturated aqueous NaHCO3 solution (3×200 mL), and water (200 mL). The organic layer was dried over Na2SO4 and the solvent was evaporated under reduced pressure. The remaining yellow solid was washed with a mixture of hexanes/diethyl ether (2×10 mL) and then with hexanes (3×5 mL) to afford N-formyl-2-methylaniline 8b as a white solid (9.70 g, 72%). 1H NMR (CDCl3, 300 MHz): δ=9.03-8.18 (m, 2H, CHO, NH), 7.77-7.03 (m, 4H), 2.30-2.22 (m, 3H); 13C{1H}NMR (CDCl3, 75 MHz): δ=164.41, 160.32, 135.50, 134.99, 131.45, 130.82, 130.50, 129.87, 127.25, 126.80, 126.34, 125.84, 123.75, 121.32, 18.05, 17.99; HRMS (FAB+) calculated for C8H10NO [M]+ 136.0762, observed 136.0783.
Reaction SMILES: C([SiH](CC)CC)C.[Br:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[C:11]([CH:19]([C:21]2[S:25][C:24]3[CH:26]=[CH:27][C:28]([CH2:30][CH3:31])=[CH:29][C:23]=3[CH:22]=2)O)[CH:10]=1.CO.O>C(Cl)Cl>[Br:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[C:11]([CH2:19][C:21]2[S:25][C:24]3[CH:26]=[CH:27][C:28]([CH2:30][CH3:31])=[CH:29][C:23]=3[CH:22]=2)[CH:10]=1
Reactant: CCc1ccc2sc(C(O)c3cc(Br)c4ccccc4c3)cc2c1
Agent: CC[SiH](CC)CC
Solvent: CO
Solvent: ClCCl
Solvent: O
Product: CCc1ccc2sc(Cc3cc(Br)c4ccccc4c3)cc2c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 61.5 %

Procedure:
In a nitrogen stream, triethylsilane (0.63 ml, 3.93 mmol) and a boron trifluoride-diethyl ether complex (0.27 ml, 2.16 mmol) were added to a solution of (4-bromo-naphthalen-2-yl)-(5-ethylbenzo[b]-thiophen-2-yl)methanol (780 mg, 1.96 mmol) in methylene chloride (20 ml) at 0° C. and the reaction mixture was stirred at room temperature for three hours. To the obtained solution was added methanol (10 ml) and water (30 ml) and the mixture was extracted with methylene chloride. The organic layer was washed with a saturated sodium chloride aqueous solution and dried (anhydrous magnesium sulfate), and then the solvent was distilled under reduced pressure. The obtained residue was purified by silica gel column chromatography [developing solution=n-hexane)] to obtain the title compound (460 mg, 62%).
Reaction SMILES: [CH2:1]([Br:7])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[C:8]1([P:14]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>C1(C)C=CC=CC=1>[Br-:7].[CH2:1]([P+:14]([C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Reactant: CCCCCCBr
Solvent: Cc1ccccc1
Product: CCCCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Product: [Br-]

Procedure:
82.5 g n-hexyl bromide and 131.2 g triphenylphosphine were boiled under reflux for 35 h in 500 ml toluene. The solvent was distilled off, the residue was taken up in dichloromethane and 1 l diethyl ether was added. Crystallisation at −15° C. gave n-hexyltriphenylphosphonium bromide (3).
Reaction SMILES: [OH:1][N:2]1[CH:5]([CH2:6][OH:7])[CH:4]([N:8]2[CH:16]=[N:15][C:14]3[C:9]2=[N:10][CH:11]=[N:12][C:13]=3[NH:17][C:18](=[O:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:3]1=[O:26].[CH3:27][O:28][C:29]1[CH:50]=[CH:49][C:32]([C:33](Cl)([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)=[CH:31][CH:30]=1>N1C=CC=CC=1>[OH:1][N:2]1[CH:5]([CH2:6][O:7][C:33]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)([C:34]2[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=2)[C:32]2[CH:31]=[CH:30][C:29]([O:28][CH3:27])=[CH:50][CH:49]=2)[CH:4]([N:8]2[CH:16]=[N:15][C:14]3[C:9]2=[N:10][CH:11]=[N:12][C:13]=3[NH:17][C:18](=[O:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:3]1=[O:26]
Reactant: COc1ccc(C(Cl)(c2ccccc2)c2ccc(OC)cc2)cc1
Reactant: O=C(Nc1ncnc2c1ncn2C1C(=O)N(O)C1CO)c1ccccc1
Solvent: c1ccncc1
Product: COc1ccc(C(OCC2C(n3cnc4c(NC(=O)c5ccccc5)ncnc43)C(=O)N2O)(c2ccccc2)c2ccc(OC)cc2)cc1
Reaction time: 8 h

Procedure:
1-N-Hydroxy-3-(N-benzoyladenin-9-yl)-4-hydroxymethyl-2-azetidinone (10 mmole) is dissolved in pyridine (20 ml) and 4,4'-dimethoxytrityl chloride (12 mmole) is added and stirred under argon for 8 hours. The reaction mixture is concentrated under reduced pressure. The crude product is purified by flash chromatorgraphy using silica gel and ethyl acetate/di-chloromethane/1% triethylamine as eluants to give the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]([C:11]1([N:14]2[CH:18]=[N:17][CH:16]=[N:15]2)[CH2:13][CH2:12]1)=[O:10].[I-].[CH3:20]CCCCCCCCCCCCC[N+](C)(C)C.[OH-].[Na+]>ClC(Cl)(Cl)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1([C:11]2([N:14]3[CH:18]=[N:17][CH:16]=[N:15]3)[CH2:12][CH2:13]2)[CH2:20][O:10]1
Reactant: CCCCCCCCCCCCCC[N+](C)(C)C
Reactant: O=C(c1ccc(Cl)cc1Cl)C1(n2cncn2)CC1
Agent: [I-]
Agent: [Na+]
Agent: [OH-]
Solvent: CC(Cl)(Cl)Cl
Product: Clc1ccc(C2(C3(n4cncn4)CC3)CO2)c(Cl)c1

Procedure:
1-(1-H-1,2,4-Triazol-1-yl)cyclopropyl 2,4-dichlorophenyl ketone (0.5 g, 1.8 mMole) was added to trimethylsulfphoxonium iodide (0.57 g, 2.6 mMole), cetrimide (0.02 g), 1,1,1-trichloroethane (10 ml) and aqueous sodium hydroxide solution (5 ml of 20%). The mixture was refluxed for twenty hours.
Reaction SMILES: [H-].[Na+].[CH2:3]([CH:6]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:4][CH3:5].[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[CH2:31][CH2:32]I)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.O>CN(C)C=O>[CH2:17]([O:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[CH2:31][CH2:32][C:6]([CH2:3][CH2:4][CH3:5])([C:7]([O:9][CH2:10][CH3:11])=[O:8])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: ICCc1ccccc1OCc1ccccc1
Reactant: CCCC(C(=O)OCC)C(=O)OCC
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCC(CCc1ccccc1OCc1ccccc1)(C(=O)OCC)C(=O)OCC
Temperature: 25 °C
Reaction time: 8 h
Yield: 82 %

Procedure:
To a suspension of sodium hydride (1.3 g) in dimethylformamide (15 ml), a solution of diethyl propylmalonate (6.6 g) in dimethylformamide (45 ml) was added under ice-cooling and the mixture was stirred at room temperature for an hour. To the solution was added a solution of 2-(2-benzyloxyphenyl)ethyl iodide (10 g) in dimethylformamide (30 ml), the mixture was stirred at the same temperature for an hour and left standing overnight. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with an aqueous sodium hydrogencarbonate solution and a saturated brine and dried over magnesium sulfate. The solvent was distilled away under reduced pressure and the residue was subjected to silica gel chromatography (eluent; hexane-ethyl acetate=8:1) to give the subject compound (10 g).
Reaction SMILES: [Li][CH:2](CC)C.C1CCCCC1.CN(CCN(C)C)C.[CH3:20][C:21]([N:24]([CH3:38])[C:25](=[O:37])[C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:27]=1[Si:33]([CH3:36])([CH3:35])[CH3:34])([CH3:23])[CH3:22].CI.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1>[CH3:23][C:21]([N:24]([CH3:38])[C:25](=[O:37])[C:26]1[C:31]([CH3:2])=[CH:30][CH:29]=[C:28]([F:32])[C:27]=1[Si:33]([CH3:34])([CH3:35])[CH3:36])([CH3:20])[CH3:22]
Reactant: CN(C(=O)c1cccc(F)c1[Si](C)(C)C)C(C)(C)C
Reactant: [Li]C(C)CC
Agent: CN(C)CCN(C)C
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Solvent: C1CCOC1
Solvent: CI
Solvent: C1CCCCC1
Product: Cc1ccc(F)c([Si](C)(C)C)c1C(=O)N(C)C(C)(C)C
Temperature: -100 °C
Yield: 99 %

Procedure:
1.3M s-BuLi in cyclohexane (31.4 mL, 41 mmol) was added dropwise to THF (100 mL) and TMEDA (5.35 g, 46 mmol), cooled to -100° C. under nitrogen with stirring. To this mixture was added dropwise the compound of Example 5 (10.45 g, 37 mmol), dissolved in a minimum amount of THF. After stirring for 10 min, MeI (15.8 g, 0.1114 mol) was injected. The mixture was stirred for 1 h and 25% citric acid (15 mL) was added. The mixture was extracted three times with ether; the ether extracts were combined and washed twice with water, dried (MgSO4), and concentrated. The crude product was purified by RC, with 1:9 ethyl acetate/hexanes. The title compound was recovered as a light yellow solid, in 99% yield. m.p. 44°-47° C.
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[CH:3]=1.[I:21]N1C(=O)CCC1=O.CCCCCC>C(#N)C>[NH2:1][C:2]1[N:6]([C:7]2[C:8]([Cl:18])=[CH:9][C:10]([C:14]([F:16])([F:15])[F:17])=[CH:11][C:12]=2[Cl:13])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[I:21]
Reactant: O=C1CCC(=O)N1I
Reactant: N#Cc1cc(N)n(-c2c(Cl)cc(C(F)(F)F)cc2Cl)n1
Solvent: CC#N
Solvent: CCCCCC
Product: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1I
Reaction time: 0.08 h

Procedure:
To a stirred solution of 5-amino-3-cyano-1-(2.6-dichloro-4-trifluoromethylphenyl)pyrazole (prepared as described in EP 295 117 A1) (5.0 g) in acetonitrile (60 ml) at room temperature was added N-iodosuccinimide (3.52 g), portionwise over a period of five minutes. Stirring was continued for 1 hr and the mixture was then evaporated to dryness to provide the crude product (8.2 g), still containing succinimide. This may be used without further purification or, if desired, purified by partitioning between dichloromethane and water, separating, drying (MgSO4) and evaporating the organic layer to produce a yellow solid. Trituration with hexane provided the title compound as a white solid, m.p. 213° C. (decomp.).
Reaction SMILES: [Na].[C:2]([O:6][C:7]([N:9]1[CH2:14][CH2:13][CH:12]([C:15]([F:18])([F:17])[F:16])[CH2:11][CH2:10]1)=[O:8])([CH3:5])([CH3:4])[CH3:3].[OH2:19]>C(OCC)(=O)C.[Ru]=O>[C:2]([O:6][C:7]([N:9]1[CH2:14][CH2:13][CH:12]([C:15]([F:18])([F:16])[F:17])[CH2:11][C:10]1=[O:19])=[O:8])([CH3:5])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)N1CCC(C(F)(F)F)CC1
Reactant: O
Agent: O=[Ru]
Agent: [Na]
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCC(C(F)(F)F)CC1=O
Reaction time: 0.33 h
Yield: 90 %

Procedure:
2.82 g (3.2 mmol) of sodium methaperiodate (NaIO4) was dissolved in 20 mL of water, followed by addition of 117 mg (0.88 mmol) of ruthenium oxide (RuO2). To The reaction, was added a solution in which 660 mg (2.6 mmol) of 4-trifluoromethyl-piperidin-1-carboxylic acid t-butyl ester dissolved in 35 mL of ethyl acetate, followed by stirring for 2 hours and 20 minutes. The reaction solution was diluted with excess ethylacetate and washed once with water and aqueous NaCl, respectively, and then dried over anhydrous magnesium sulfate and filtered off. The filtrated solution was distilled off under reduced pressure, then the residue was purified by column chromatography (2:1 hexane:ethyl acetate) to give 0.63 g of the title compound in a yield of 90%.
Reaction SMILES: [CH:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH:10]1[C:13]([CH3:15])([CH3:14])[C:12]([CH3:17])([CH3:16])[C:11]1=[O:18].[C-:19]#[N:20].CCCCCCC>O>[CH3:17][C:12]1([CH3:16])[C:13]([CH3:14])([CH3:15])[CH:10]1[C:11]([O:8][CH:1]([C:19]#[N:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:18]
Reactant: [C-]#N
Reactant: O=Cc1ccccc1
Reactant: CC1(C)C(=O)C(Cl)C1(C)C
Solvent: O
Solvent: CCCCCCC
Product: CC1(C)C(C(=O)OC(C#N)c2ccccc2)C1(C)C
Temperature: 70 °C

Procedure:
A 50-ml round-bottomed flask provided with a magnetic stirrer was charged with 10 mmol of benzaldehyde, 10 mmol of 2-chloro-3,3,4,4-tetramethylcyclobutanone, 12 mmol of a cyanide, 20 ml of n-heptane and 1 ml of water. The rection mixture was stirred vigorously at a temperature of 70° C. Two experiments were carried out in this manner. Table III states the cyanides used and presents the yields of the alpha-cyanobenzyl 2,2,3,3-tetramethylcyclopropane-carboxylate formed.
Reaction SMILES: [N+:1]([O-:17])([O:3][CH:4]([C:6]1[CH:11]=[C:10]([N+:12]([O-])=O)[C:9]([F:15])=[CH:8][C:7]=1[Cl:16])[CH3:5])=[O:2].[C:18](OC(=O)C)(=[O:20])[CH3:19].[H][H].Cl>[Pt]=O.O.C(OCC)(=O)C>[N+:1]([O-:17])([O:3][CH:4]([C:6]1[CH:11]=[C:10]([NH:12][C:18]([CH3:19])=[O:20])[C:9]([F:15])=[CH:8][C:7]=1[Cl:16])[CH3:5])=[O:2]
Reactant: CC(=O)OC(C)=O
Reactant: CC(O[N+](=O)[O-])c1cc([N+](=O)[O-])c(F)cc1Cl
Reactant: [H][H]
Agent: O=[Pt]
Agent: Cl
Solvent: O
Solvent: CCOC(C)=O
Product: CC(=O)Nc1cc(C(C)O[N+](=O)[O-])c(Cl)cc1F
Temperature: 25 °C
Reaction time: 2 h

Procedure:
In a Parr hydrogenation apparatus were placed 3.7 g (0.014 mole) of 1-(2-chloro-4-fluoro-5-nitrophenyl)ethyl nitrate, 0.35 g of platinum oxide catalyst, 35 ml of ethyl acetate, and 10 ml of acetic anhydride. The apparatus was pressurized with hydrogen, and the reaction was allowed to continue until the pressure ceased dropping. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure leaving a residue. This residue was mixed with 15 ml of water and 5 ml of 10% hydrochloric acid. This mixture was stirred at room temperature for two hours. Following dilution with water, the mixture was extracted with methylene chloride. The extracts were combined and washed successively with water, 5% hydrochloric acid, and a saturated, aqueous solution of sodium bicarbonate. This solution was dried, filtered, and the solvent was evaporated under reduced pressure leaving a residue. This residue was passed through a column of silica gel, eluting first with ethyl acetate/heptane (1/4) and then with ethyl acetate/heptane (1/1). The appropriate fractions were collected, and the solvent was evaporated under reduced pressure yielding 1.7 g of 1-(2-chloro-4-fluoro-5-methylcarbonylaminophenyl)ethyl nitrate as a white solid. The nmr and ir spectra were consistent with the proposed structure.
Reaction SMILES: [OH:1][CH:2]1[CH2:14][C:13]2[C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[N:6]([CH3:15])[C:5]=2[CH2:4][CH2:3]1.[S:16](Cl)([C:19]1[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=1)(=[O:18])=[O:17].CC1C=C2C(=CC=1)NC1CCC(OS(C3C=CC(C)=CC=3)(=O)=O)CC2=1>>[CH3:15][N:6]1[C:5]2[CH2:4][CH2:3][CH:2]([O:1][S:16]([C:19]3[CH:25]=[CH:24][C:22]([CH3:23])=[CH:21][CH:20]=3)(=[O:18])=[O:17])[CH2:14][C:13]=2[C:12]2[C:7]1=[CH:8][CH:9]=[CH:10][CH:11]=2
Reactant: Cn1c2c(c3ccccc31)CC(O)CC2
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: Cc1ccc(S(=O)(=O)OC2CCc3[nH]c4ccc(C)cc4c3C2)cc1
Product: Cc1ccc(S(=O)(=O)OC2CCc3c(c4ccccc4n3C)C2)cc1

Procedure:
The 9-methyl-3-tosyloxy-1,2,3,4-tetrahydrocarbazole was prepared from 49 g. of 3-hydroxy-9-methyl-1,2,3,4-tetrahydrocarbazole and 49 g. of tosyl chloride using the procedure described in Example 21 for the preparation of 6-methyl-3-tosyloxy-1,2,3,4-tetrahydrocarbazole. There was thus obtained 81 g. of 9-methyl-3-tosyloxy-1,2,3,4-tetrahydrocabazole which melted at 155°-157°C.