Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[C:9]([OH:13])[CH:10]=[CH:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N+:14]([O-])([OH:16])=[O:15]>C(O)(=O)C>[N+:14]([C:10]1[CH:11]=[CH:12][C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[CH:8][C:9]=1[OH:13])([O-:16])=[O:15]
Reactant: O=[N+]([O-])O
Reactant: Oc1cccc(-c2ccccc2)c1
Solvent: CC(=O)O
Product: O=[N+]([O-])c1ccc(-c2ccccc2)cc1O

Procedure:
A solution of 3-phenyl phenol (2 g, 11 mmol) in acetic acid was treated with concentrated nitric acid drop-wise until all starting material was consumed. The solution was partitioned between water and methylene chloride. The organic phase was separated and the aqueous phase was extracted once more with methylene chloride. The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate/hexanes) to afford desired (1.2 g, 50%). 1H NMR (CDCl3): d 10.65(s, 1H), 8.18 (d, 1H, J=10.0 Hz), 7.65 (d, 2H, J=6.0 Hz), 7.49 (m, 3H), 7.34 (s, 1H), 7.10 (d, 1H, J=10.0 Hz).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[CH2:8]([C:12]1[O:16][N:15]=[C:14]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[CH:13]=1)[CH2:9][C:10]#[CH:11]>>[F:23][C:20]1[CH:19]=[CH:18][C:17]([C:14]2[CH:13]=[C:12]([CH2:8][CH2:9][C:10]#[C:11][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=3)[O:16][N:15]=2)=[CH:22][CH:21]=1
Reactant: Brc1ccccn1
Reactant: C#CCCc1cc(-c2ccc(F)cc2)no1
Product: Fc1ccc(-c2cc(CCC#Cc3ccccn3)on2)cc1
Yield: 25 %

Procedure:
The title compound was prepared in accordance with the general method of Example 1, from 2-bromo-pyridine (40 mg, 0.26 mmol) and 5-but-3-ynyl-3-(4-fluoro-phenyl)-isoxazole (55 mg, 0.26 mmol). Reaction time: 2 hours. The crude residue was purified by flash chromatography (cyclohexane/AcOEt 9:1 to 7:3) to yield 19 mg (65 μmol, 25%) of 2-(4-(3-(4-fluorophenyl)isoxazol-5-yl)but-1-ynyl)pyridine as a white solid (M.P.=83-84° C.).
Reaction SMILES: O1CCCCC1[O:7][CH:8]([C:10]#[C:11][C:12]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=1)[CH3:9].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+]>C(O)C>[OH:7][CH:8]([C:10]#[C:11][C:12]1[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=1)[CH3:9]
Reactant: CC(C#Cc1ccc(Cl)cc1)OC1CCCCO1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: CC(O)C#Cc1ccc(Cl)cc1

Procedure:
The product prepared in step (c) above (0.05 mol) and p-toluenesulphonic acid (1 g) dissolved in ethanol (50 ml) is refluxed for 3 hours. After cooling, 2 to 3 g potassium carbonate is added and the mixture is filtered. The ethanol is removed in vacuo and the residue is taken up in ether/water (40 ml/10 ml). The ether layer is washed, dried and the ether is removed in vacuo. The residue is distilled to afford the title compound in almost quantitative yield.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(O)C.[CH2:19]([NH:21][CH2:22]C)C.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[CH3:19][N:21]([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH3:22]
Reactant: CCNCC
Reactant: BrCCCCCCCCc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: CCOC(C)=O
Product: CN(C)CCCCCCCCc1ccccc1
Temperature: 25 °C
Reaction time: 7.5 h

Procedure:
To 538 mg of (8-bromooctyl)benzene were added 1 ml of ethanol and 1.05 ml of 50% aqueous diethylamine solution, and the mixture was stirred at a room temperature for 7.5 hours. To the mixture were added 30 ml of ethyl acetate and 5 ml of 5% sodium bicarbonate aqueous solution, and the resulting layers were separated. The organic layer was washed with water and a saturated sodium chloride aqueous solution, dried over magnesium sulfate, and evaporated under a reduced pressure. The residue was applied to a silica gel column and eluted with chloroform/methanol (9:1) to eliminate impurities appeared on the start point on thin layer chromatography. In this way, compound as colorless liquid, 378 mg of the title compound was obtained as colorless liquid.
Reaction SMILES: Cl[O-].[Na+].C(N(CC)CC)C.[Br:11][C:12]1[CH:20]=[CH:19][C:15](/[CH:16]=[N:17]/[OH:18])=[C:14]([O:21][CH2:22][C:23]#[C:24][C:25]2[C:29]([C:30]([F:33])([F:32])[F:31])=[C:28]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[O:27][N:26]=2)[CH:13]=1>ClCCl>[Br:11][C:12]1[CH:20]=[CH:19][C:15]2[C:16]3=[N:17][O:18][C:24]([C:25]4[C:29]([C:30]([F:33])([F:31])[F:32])=[C:28]([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=5)[O:27][N:26]=4)=[C:23]3[CH2:22][O:21][C:14]=2[CH:13]=1
Reactant: O/N=C/c1ccc(Br)cc1OCC#Cc1noc(-c2ccccc2)c1C(F)(F)F
Agent: [Na+]
Agent: [O-]Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: FC(F)(F)c1c(-c2onc3c2COc2cc(Br)ccc2-3)noc1-c1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 72.7 %

Procedure:
To a mixture of sodium hypochlorite (23 mL), triethylamine (Preparation 62E, 0.021 mL, 0.155 mmol), and dichloromethane (1.0 mL) at 0° C. was added dropwise a solution of (E)-4-bromo-2-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)prop-2-ynyloxy)benzaldehyde oxime (0.036 g, 0.077 mmol) in dichloromethane (3 mL). The reaction mixture was stirred at 0° C. for 30 min. and then at room temperature for 1.5 h. The reaction mixture was diluted with dichloromethane, and the organic layer was collected. The aqueous layer was extracted with dichloromethane (2×), and the combined organic layers were washed with brine and dried over anhydrous sodium sulfate. Concentration under reduced pressure followed by trituration with methanol with sonication afforded 7-bromo-3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4H-chromeno[4,3-c]isoxazole (0.026 g, 0.056 mmol, 73% yield) as a white solid. The product had an HPLC ret. time=3.91 min.−Column: Chromolith SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=464.9. 1H NMR (500 MHz, CDCl3) δ ppm 5.49 (s, 2H), 7.23-7.27 (m, 2H), 7.55-7.59 (m, 2H), 7.60-7.65 (m, 1H), 7.73 (d, J=7.49 Hz, 2H), and 7.78 (d, J=8.05 Hz, 1H).
Reaction SMILES: Br[CH2:2][C:3]1[C:4]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=2)=[N:5][C:6]2[C:11]([C:12]=1[C:13]([O:15][CH3:16])=[O:14])=[CH:10][C:9]([S:17]([CH2:20][CH3:21])(=[O:19])=[O:18])=[C:8]([O:22][CH2:23][CH3:24])[CH:7]=2.[NH:35]1[CH2:40][CH2:39][CH:38]([N:41]2[CH2:46][CH2:45][O:44][CH2:43][CH2:42]2)[CH2:37][CH2:36]1>C(#N)C>[CH2:23]([O:22][C:8]1[CH:7]=[C:6]2[C:11]([C:12]([C:13]([O:15][CH3:16])=[O:14])=[C:3]([CH2:2][N:35]3[CH2:40][CH2:39][CH:38]([N:41]4[CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)[CH2:37][CH2:36]3)[C:4]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:32])([F:34])[F:33])[CH:26]=3)=[N:5]2)=[CH:10][C:9]=1[S:17]([CH2:20][CH3:21])(=[O:18])=[O:19])[CH3:24]
Reactant: CCOc1cc2nc(-c3cccc(C(F)(F)F)c3)c(CBr)c(C(=O)OC)c2cc1S(=O)(=O)CC
Reactant: C1CC(N2CCOCC2)CCN1
Solvent: CC#N
Product: CCOc1cc2nc(-c3cccc(C(F)(F)F)c3)c(CN3CCC(N4CCOCC4)CC3)c(C(=O)OC)c2cc1S(=O)(=O)CC
Reaction time: 3 h
Yield: 51 %

Procedure:
A suspension of methyl 3-(bromomethyl)-7-(ethyloxy)-6-(ethylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (3.54 g, 6.31 mmol) and 4-(4-piperidinyl)morpholine (1.397 g, 8.20 mmol) in acetonitrile (30 mL) was stirred for 3 h. The solvent was removed under reduced pressure, and the residue was diluted with NaHCO3 and extracted with methylene chloride (three times). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was dissolved in DMF and purified via HPLC (Biotage RP, 0-50% MeCN/H2O with 0.1% TFA). The fractions containing the product were neutralized with saturated aqueous NaHCO3 and extracted with methylene chloride (three times). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated to afford methyl 7-(ethyloxy)-6-(ethylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (2.09 g, 51% yield). 1H NMR (400 MHz, DMSO-d6) δ8.37 (s, 1H), 7.97 (s, 1H), 7.90 (t, J=8.53 Hz, 2H), 7.76-7.81 (m, 2H), 4.39 (q, J=6.94 Hz, 2H), 4.01 (s, 3H), 3.50-3.64 (m, 9H), 2.63 (d, J=11.29 Hz, 2H), 2.38 (br. s., 4H), 1.95-2.05 (m, 1H), 1.81 (t, J=11.17 Hz, 2H), 1.61 (d, J=11.54 Hz, 2H), 1.45 (t, J=7.03 Hz, 3H), 1.19-1.30 (m, 2H), 1.15 (t, J=7.40 Hz, 3H); MS (m/z) 650.2 (M+H+).
Reaction SMILES: C(Cl)(=O)C(Cl)=O.CS(C)=O.[Cl:11][C:12]1[N:13]=[C:14]([CH2:21][OH:22])[CH:15]=[C:16]2[CH:20]=[CH:19][O:18][C:17]=12.C(=O)=O.CC(C)=O>C(Cl)Cl>[Cl:11][C:12]1[N:13]=[C:14]([CH:21]=[O:22])[CH:15]=[C:16]2[CH:20]=[CH:19][O:18][C:17]=12
Reactant: OCc1cc2ccoc2c(Cl)n1
Agent: O=C(Cl)C(=O)Cl
Agent: O=C=O
Solvent: CC(C)=O
Solvent: ClCCl
Solvent: CS(C)=O
Product: O=Cc1cc2ccoc2c(Cl)n1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 97 %

Procedure:
Oxalyl chloride (3.1 mL, 35 mmol) is dissolved in 200 mL CH2Cl2 in a dried flask under N2. The flask is placed in a dry-ice/acetone bath at −78° C., DMSO (4.95 mL, 70 mmol) in 10 mL CH2Cl2 is added drop-wise, and the mixture is stirred for 20 min. (7-Chlorofuro[2,3-c]pyridin-5-yl)methanol (C4) (5.5 g, 30 mmol) in 10 mL CH2Cl2 is added, and the reaction is stirred 30 min at −78° C. TEA (21.3 mL, 153 mmol) is then added. The reaction is stirred 30 min in the dry-ice/acetone bath, an ice bath replaces the dry-ice/acetone bath, and the reaction is stirred 1 h and is washed with 100 mL 1:1 saturated NaCl/NaHCO3. The organic layer is dried over anhydrous K2CO3, filtered, and concentrated in vacuo to afford 7-chlorofuro[2,3-c]pyridine-5-carbaldehyde (C6) as a pale yellow solid (97% yield). MS (EI) for C8H4ClNO2 m/z: 181 (M)+.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5](I)=[C:4]([F:9])[CH:3]=1.[CH2:10]([N:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:11]#[CH:12].C(N(CC)CC)C.[Cl-].[NH4+]>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:12]#[C:11][CH2:10][N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)=[C:4]([F:9])[CH:3]=1
Reactant: Fc1cc(Br)ccc1I
Reactant: C#CCN1CCCCC1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: [Cl-]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: Fc1cc(Br)ccc1C#CCN1CCCCC1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 44.7 %

Procedure:
To a solution of 1-bromo-3-fluoro-4-iodobenzene (2.5 g), 1-prop-2-ynylpiperidine (1.5 g), dichlorobis(triphenylphosphine)palladium(II) (300 mg) and copper(I) iodide (40 mg) in N,N-dimethylformamide (20 ml) was added triethylamine (10 ml) under a nitrogen atmosphere, and the solution was stirred for 1.5 hours at room temperature. A saturated aqueous solution of ammonium chloride was added thereto followed by stirring, the solution was extracted with ethyl acetate, then sequentially washed with water and brine, and dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified by NH silica gel column chromatography (hexane-ethyl acetate system) to provide the title compound (1.1 g).
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[H-].[Na+].Cl[C:9]1[C:14]([I:15])=[CH:13][N:12]=[CH:11][N:10]=1>C1COCC1>[N:1]1([C:9]2[C:14]([I:15])=[CH:13][N:12]=[CH:11][N:10]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: c1c[nH]cn1
Reactant: Clc1ncncc1I
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Ic1cncnc1-n1ccnc1
Reaction time: 0.25 h
Yield: 52 %

Procedure:
To a solution of 1H-imidazole (0.085 g, 1.248 mmol) in THF (Volume: 10 mL) was added sodium hydride (0.062 g, 1.560 mmol). After 15 minutes at room temperature, 4-chloro-5-iodopyrimidine (0.25 g, 1.040 mmol) was added as a solution in THF (5 mL). After 2 h at room temperature, the reaction was quenched with water. The reaction mixture was extracted with EtOAc (3×). The combined organics were dried over MgSO4, filtered and concentrated to give the title compound (0.155 g, 0.541 mmol, 52.1% yield) as a pale yellow solid. ESI MS (M+H)+=273.0.
Reaction SMILES: [Cl:1][C:2]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[C:7]([N+]([O-])=O)[CH:6]=1.[CH3:25][P:26]([O:30]CC)[O:27][CH2:28][CH3:29]>C(#N)C>[CH3:25][P:26]([C:7]1[CH:6]=[C:5]([O:4][C:3]2[CH:17]=[CH:18][C:19]([C:21]([F:24])([F:23])[F:22])=[CH:20][C:2]=2[Cl:1])[CH:10]=[CH:9][C:8]=1[N+:11]([O-:13])=[O:12])(=[O:30])[O:27][CH2:28][CH3:29]
Reactant: CCOP(C)OCC
Reactant: O=[N+]([O-])c1ccc(Oc2ccc(C(F)(F)F)cc2Cl)cc1[N+](=O)[O-]
Solvent: CC#N
Product: CCOP(C)(=O)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 4-(2-chloro-4-trifluoromethylphenoxy)-1,2-dinitrobenzene (0.9 g, 2.48 mmol), diethyl methylphosphonite (0.5 g, 3.72 mmol) and acetonitrile (3 ml) is stirred at room temperature overnight. The reaction mixture is concentrated to dryness, and the residue is purified by preparative thin layer chromatography (silica gel, eluting with 50% ethyl acetate/hexane) to give ethyl P-methyl-2-nitro-5-(2-chloro-4-trifluoromethylphenoxy)phenylphosphinate.
Reaction SMILES: [Li+].CC([N-]C(C)C)C.C(NC(C)C)(C)C.C[Si](C=[N+]=[N-])(C)C.[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][C:33](=O)[CH2:32][CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24].C1C[O:40][CH2:39]C1>>[CH:39]([CH:33]1[CH2:34][CH2:35][N:30]([C:28]([O:27][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:29])[CH2:31][CH2:32]1)=[O:40]
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: C1CCOC1
Agent: CC(C)[N-]C(C)C
Agent: C[Si](C)(C)C=[N+]=[N-]
Agent: [Li+]
Solvent: CC(C)NC(C)C
Product: CC(C)(C)OC(=O)N1CCC(C=O)CC1
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
To a solution of 15.9 mL of LDA (2 M solution in THF) in 25 mL of THF at −78° C. was added 36.6 mL of diisopropylamine followed by 15.9 ml of (trimethylsilyl)diazomethane dropwise. After stirring at −78° C. for 30 min, 5.25 g of tert-butyl-4oxo-1-piperidinecarboxylate in 10 mL of THF was added slowly over 10 min. The reaction was stirred at −78° C. for 1 hr. After refluxing for 4 hr, the reaction was quenched with cold water and extracted with 3×70 mL of EtOAc. The combined organic phases were dried over MgSO4 and concentrated. The residue was dissolved in 150 mL of EtOAc, then 10 g of silica gel was added. After stirring at rt for 16 hr, silica gel was filtered off. Concentration of filtrate followed by flash chromatography eluting with 25% EtOAc in hexane followed by 100% EtOAc afforded 3.66 g of the title compound as an oil.
Reaction SMILES: C([Sn](CCCC)(OCCCC)[O:6][Sn:7]([CH2:17][CH2:18][CH2:19][CH3:20])([CH2:13][CH2:14][CH2:15][CH3:16])[O:8][CH2:9][CH2:10][CH2:11][CH3:12])CCC.[CH2:30](O)[CH2:31][CH2:32][CH3:33]>CCCCCC>[CH2:17]([Sn:7]([CH2:13][CH2:14][CH2:15][CH3:16])([O:6][CH2:30][CH2:31][CH2:32][CH3:33])[O:8][CH2:9][CH2:10][CH2:11][CH3:12])[CH2:18][CH2:19][CH3:20]
Reactant: CCCCO
Reactant: CCCCO[Sn](CCCC)(CCCC)O[Sn](CCCC)(CCCC)OCCCC
Solvent: CCCCCC
Product: CCCCO[Sn](CCCC)(CCCC)OCCCC
Temperature: 140 °C
Reaction time: 0.1 h
Yield: 54 %

Procedure:
A feed pump was used to start feeding the starting material 1,1,3,3-tetrabutyl-1,3-di(butyloxy)-distannoxane prepared in the same manner as in Example 12 from supply line 93 at 280 g/Hr and the reactant 1-butanol (manufactured by Wako Pure Chemical Industries Ltd., Japan, industrial product) from supply line 94 at 1,330 g/Hr. The holding time in the reactor was 6 minutes. A pump was used to supply hexane (manufactured by Wako Pure Chemical Industries Ltd., Japan, dehydration grade) at 300 g/Hr from the organic solvent supply line 96 to the reactor lower portion 102, wherein accumulated reaction solution was circulated at 6,000 g/Hr by the circulation line 97 and the reboiler 98 while heating at a temperature of about 140° C. The liquid temperature inside the reactor was 140° C., and the pressure of the back pressure valve 106 was adjusted to 0.12 MPa-G. Continuous supply was continued in this state for 10 hours, after which the system reached a steady state. Low boiling point components flowed from the reactor upper portion 101 and through the low boiling point component recovery line 103 for liquefaction at the condenser 104, and were thereby recovered from the liquid-phase recovery line 108 at 1,088 g/Hr. Furthermore, from the reactor lower portion 102, a dibutyltin alkoxide-containing component was recovered at 821 g/Hr from the extraction line 109. Analysis of the recovered liquid showed that using dibutyltin oxide as a reference, the liquid contained a dibutyltin alkoxide consisting of a yield of about 54.0% dibutyl-di(butyloxy)tin and 46.0% of 1,1,3,3-tetrabutyl-1,3-di(butyloxy)-distannoxane. Tributyltin butoxide had a yield of 0.013%. Meanwhile, the liquid recovered from the liquid-phase recovery line 108 was transparent and contained 2,500 ppm of moisture. The dehydration rate in the column reactor was 0.24 mol/Hr, which was greater than the value 0.00037 mol/Hr calculated from expression (16).
Reaction SMILES: [CH2:1]([C:4]1[C:9]([O:10][CH3:11])=[CH:8][C:7]([OH:12])=[C:6]([F:13])[CH:5]=1)[CH:2]=[CH2:3]>CCO.[Pd]>[F:13][C:6]1[CH:5]=[C:4]([CH2:1][CH2:2][CH3:3])[C:9]([O:10][CH3:11])=[CH:8][C:7]=1[OH:12]
Reactant: C=CCc1cc(F)c(O)cc1OC
Agent: [Pd]
Solvent: CCO
Product: CCCc1cc(F)c(O)cc1OC
Reaction time: 6 h
Yield: 86.7 %

Procedure:
4-Allyl-2-fluoro-5-methoxyphenol (5.16 g, 28.3 mmol) was dissolved in EtOH (150 mL) and Pd/C (5%, 250 mg) was added. Hydrogenation for 6 h at room temperature and atmospheric pressure, addition of more Pd/C (5%,100 mg), continued reaction for 3 h followed by removal of the catalyst and evaporation of the solvent gave 2-fluoro-5-methoxy-4-propylphenol (4.52 g) as an oil. 1H NMR (DMSO-d6): δ 9.53 (s, 1 H), 6.85 (d, J=11.8 Hz, 1 H), 6.51 (d, J=7.7 Hz, 1 H), 3.67 (s, 3 H), 2.38 (t, J=7.5 Hz, 2 H), 1.46 (m, J=7.5 Hz, 2 H), 0.84 (t, J =7.4 Hz, 3 H). 13C MNR (DMSO-d6): δ153.21, 144.84 (d, J=230 HZ), 142.70 (d, J=13 Hz), 120.41 (d, J=5 Hz), 116.46 (d, J=19 Hz), 101.25, 55.62, 30.68, 22.61, 13.71. MS (EI, 70 eV): m/z (rel.int.) 184 (M+,69).
Reaction SMILES: ClC1CCCNC(=O)C1.C[O-].[Na+].[C:13]([N:21]1[CH2:26][CH2:25]O[CH2:23][C:22]1=[O:27])(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH3:28][O:29][CH:30]1[CH2:37][CH2:36][CH2:35][NH:34][C:32](=[O:33])[CH2:31]1>>[CH3:28][O:29][CH:30]1[CH2:37][CH2:36][CH2:35][NH:34][C:32](=[O:33])[CH2:31]1.[C:13]([N:21]1[CH2:26][CH2:25][CH2:31][CH:30]([O:29][CH3:28])[CH2:23][C:22]1=[O:27])(=[O:20])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: O=C1COCCN1C(=O)c1ccccc1
Agent: COC1CCCNC(=O)C1
Agent: C[O-]
Agent: O=C1CC(Cl)CCCN1
Product: COC1CCCN(C(=O)c2ccccc2)C(=O)C1

Procedure:
3-Methoxycaprolactam was prepared from 3-chlorocaprolactam (prepared as described in Francis, et al. J. Am. Chem. Soc. 1958, 80, 6238) and sodium methoxide according to the method of Kondelikova, et al. (Collect. Czech. Chem. Commun. 1971, 36(9), 3391). The desired product N-benzoyl-3-methoxycaprolactam is synthesized as for N-benzoyl-3-oxomorpholine (Example I) using 3 -methoxycaprolactam in place of morpholin-3-one.
Reaction SMILES: [CH:1]12[C:9](=[O:10])[O:8][C:6](=O)[CH:3]([CH2:4][CH2:5]1)[CH2:2]2.[NH2:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][N:19]([C:22]2[N:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[CH2:18][CH2:17]1>ClCCl>[N:23]1[CH:24]=[CH:25][CH:26]=[N:27][C:22]=1[N:19]1[CH2:20][CH2:21][N:16]([CH2:15][CH2:14][CH2:13][CH2:12][N:11]2[C:6](=[O:8])[CH:3]3[CH2:2][CH:1]([CH2:5][CH2:4]3)[C:9]2=[O:10])[CH2:17][CH2:18]1
Reactant: NCCCCN1CCN(c2ncccn2)CC1
Reactant: O=C1OC(=O)C2CCC1C2
Solvent: ClCCl
Product: O=C1C2CCC(C2)C(=O)N1CCCCN1CCN(c2ncccn2)CC1

Procedure:
1,3-Cyclopentanedicarboxylic acid (4.0 g., 25 mmole) was converted to the anhydride by refluxing for 3 hours in 20 ml. of acetic anhydride. After removal of excess acetic anhydride, extraction with hexane and evaporation of the hexane, 3.95 g. of cyclopentane-1,3-dicarboxylic anhydride was obtained. The anhydride was combined with 6.51 g. (27 mmole) of 1-(4-aminobutyl)-4-(2-pyrimidinyl)piperazine in 50 ml. of dichloromethane and stirred at room temperature overnight. The dichloromethane was removed in vacuo and replaced with 75 ml. of toluene. The mixture was refluxed for 24 hours with water separation via a Dean-Stark trap. The product was concentrated under vacuum and chromatographed on 200 g. of silica gel with 5% ethanol/chloroform. The product-containing fractions were combined and concentrated and the residue crystallized (2 crops) from isopropanol with addition of 4N HCl/isopropanol. A second recrystallization from isopropanol gave 1.1 g. of the title compound as the dihydrochloride, hemihydrate; m.p. 201°-203° C.(d).
Reaction SMILES: [CH2:1]([CH:3]1[C:8](=[O:9])[CH2:7][CH2:6][CH2:5][C:4]1=[O:10])[CH3:2].N1C=CC=CC=1.C(N(CC)[CH2:20][CH2:21][C:22](=[O:34])[CH2:23][CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([O:32][CH3:33])[CH:27]=1)C.COC1C=C(CCCC(=O)C=C)C=CC=1>C1C=CC=CC=1>[CH3:33][O:32][C:28]1[CH:27]=[C:26]([CH2:25][CH2:24][CH2:23][C:22](=[O:34])[CH2:21][CH2:20][C:3]2([CH2:1][CH3:2])[C:8](=[O:9])[CH2:7][CH2:6][CH2:5][C:4]2=[O:10])[CH:31]=[CH:30][CH:29]=1
Reactant: CCN(CC)CCC(=O)CCCc1cccc(OC)c1
Reactant: CCC1C(=O)CCCC1=O
Agent: C=CC(=O)CCCc1cccc(OC)c1
Solvent: c1ccncc1
Solvent: c1ccccc1
Product: CCC1(CCC(=O)CCCc2cccc(OC)c2)C(=O)CCCC1=O

Procedure:
Reflux 2-ethylcyclohexane-1,3-dione (30.6 g), pyridine (20 cc), benzene (372 cc) and a mixture of 1-diethylamino-6-m-methoxyphenylhexan-3-one and 6-m-methoxyphenylhex-1-en-3-one (40.3 g, produced by the distillation of the former substance) for 15 hours. Wash the cooled reaction mixture with water, 10% aqueous sulfuric acid, water, 10% aqueous sodium carbonate, water and brine, and filter. Evaporate the solvent to leave as residue 2-(6-m-methoxyphenyl-3-oxohexyl)-2-ethylcyclohexane-1,3-dione, 38.1 g, 56.2%.
Reaction SMILES: I[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][CH:5]=1.C([Sn](CCCC)(CCCC)[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][C:18]=1[N+:25]([O-:27])=[O:26])CCC.O1CCCC1>CN1CCCC1=O.S1C=CC=C1C([O-])=O.[Cu+]>[CH3:24][O:23][C:20]1[CH:21]=[CH:22][C:17]([CH:2]=[CH:3][C:4]2[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][CH:5]=2)=[C:18]([N+:25]([O-:27])=[O:26])[CH:19]=1
Reactant: COc1ccc(C=CI)cc1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccc(OC)cc1[N+](=O)[O-]
Agent: [Cu+]
Agent: O=C([O-])c1cccs1
Solvent: C1CCOC1
Solvent: CN1CCCC1=O
Product: COc1ccc(C=Cc2ccc(OC)cc2[N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 0.42 h
Yield: 72.8 %

Procedure:
By referring to the synthetic method of J. Org. Chem., 1997, 62, 199, to a solution of lithium acetate (280 mg) in water (3 ml) was added acetonitrile (90 ml), the solution was stirred at room temperature, then 4-methoxycinnamic acid (7.5 g), N-iodosuccinimide (10 g) were sequentially added thereto, the solution was stirred for 2 hours at room temperature, and then neutralized with a saturated aqueous solution of sodium bicarbonate. The solution was extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified by silica gel column chromatography (hexane-ethyl acetate system) to provide 1-(2-iodovinyl)-4-methoxybenzene (8.0 g). By referring to the synthetic method of J. Am. Chem. Soc., 1996, 118, 2748, to a solution of 1-(2-iodovinyl)-4-methoxybenzene (7.1 g) and tributyl(4-methoxy-2-nitrophenyl)tin (10 g) in 1-methyl-2-pyrrolidone (100 ml) was added copper(I) thiophene-2-carboxylate (6.6 g) on an ice bath under a nitrogen atmosphere, and the solution was stirred for 25 minutes at room temperature. Tetrahydrofuran was added thereto, the solution was stirred, then filtered through alumina, extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified by silica gel column chromatography (hexane-ethyl acetate system) to provide the title compound (4.7 g).