Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]([CH3:21])[NH:3][C:4]1[C:9]([N+:10]([O-:12])=[O:11])=[CH:8][C:7]([C:13]([F:16])([F:15])[F:14])=[C:6](Cl)[C:5]=1[N+:18]([O-:20])=[O:19].[NH3:22].C(O)C.C(=O)=O.CC(C)=O>O>[CH3:1][N:2]([NH:3][C:4]1[C:5]([N+:18]([O-:20])=[O:19])=[C:6]([NH2:22])[C:7]([C:13]([F:16])([F:15])[F:14])=[CH:8][C:9]=1[N+:10]([O-:12])=[O:11])[CH3:21]
Reactant: CN(C)Nc1c([N+](=O)[O-])cc(C(F)(F)F)c(Cl)c1[N+](=O)[O-]
Reactant: N
Agent: O=C=O
Solvent: CCO
Solvent: CC(C)=O
Solvent: O
Product: CN(C)Nc1c([N+](=O)[O-])cc(C(F)(F)F)c(N)c1[N+](=O)[O-]
Temperature: 65 °C
Reaction time: 8 h

Procedure:
A 50 ml. Pyrex ampule was charged with N-dimethylamino-3-chloro-2,6-dinitro-4-trifluoromethylaniline (5.0 g.; 0.015 mole), ethanolic ammonia (8.54 g. of 6.06% w/w solution; 0.03 mole) and enough absolute ethanol to bring the liquid level to within one inch of the neck. The ampule was chilled in a bath of dry ice-acetone, sealed, heated with hot water (65°-75° C.) until the starting material was in solution, and then placed in an oven at 65° C. After heating at 65° C. for 72 hours, the ampule was opened and the reaction mixture was transferred to a flask and evaporated to dryness under vacuum. Cyclohexane (200 ml.) was added to the residue. The resultant mixture was heated under reflux for one hour, then filtered hot and allowed to cool to 40° C., at which temperature the product began to crystallize. The solution was decanted away from a small amount of solids and the product was allowed to crystallize slowly from the decantate by standing at room temperature overnight. The crystalline product was collected by filtration to obtain 2.7 g., m.p. 150°-153.5° C.
Reaction SMILES: [F:1][C:2]1[C:10]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=2)=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].I[CH2:18][CH3:19].[BH4-].[Na+]>C(=O)([O-])[O-].[Na+].[Na+]>[CH2:18]([N:14]1[CH2:15][CH:16]=[C:11]([C:10]2[C:2]([F:1])=[C:3]([CH:7]=[CH:8][CH:9]=2)[C:4]([NH2:6])=[O:5])[CH2:12][CH2:13]1)[CH3:19]
Reactant: CCI
Reactant: NC(=O)c1cccc(-c2ccncc2)c1F
Agent: O=C([O-])[O-]
Agent: [BH4-]
Agent: [Na+]
Product: CCN1CC=C(c2cccc(C(N)=O)c2F)CC1
Temperature: 100 °C
Reaction time: 1 h

Procedure:
To neat 2-fluoro-3-pyridin-4-yl-benzamide (0.94 g, 4.34 mmol) was added 1-iodoethane (3 ml) and the resulting mixture was heated at 100° C. for 2 h. Excess 1-iodopropane was evaporated under reduced pressure and ethanol (40 ml) was added. The mixture was cooled to −20° C. and sodium borohydride (1.25 g, 34.8 mmol) was added in portions. The resulting mixture was stirred for 1 h, after which aqueous sodium carbonate (10%, 50 ml) was added. The aqueous phase was extracted with ethylacetate (3×100 ml) and the combined organic phases was dried (MgSO4), filtered and evaporated to dryness. The residue was purified by flash column chromatography (ethylacetate/methanol, 1:1) to give the title compound (0.75 g). MS m/z (rel. intensity, 70 eV) 248 (M+, bp), 247 (37), 233 (99), 146 (22), 110 (41).
Reaction SMILES: [C:1]1([CH2:11][CH2:12][C@H:13]2[CH2:18][NH:17][CH2:16][CH2:15][NH:14]2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[CH3:19][C:20]1[S:29][C:28]2[NH:27][C:26]3[CH:30]=[CH:31][CH:32]=[CH:33][C:25]=3[N:24]=[C:23](N)[C:22]=2[CH:21]=1.C1(C)C=CC=CC=1.C(N(C(C)C)C(C)C)C>C(OCC)(=O)C.O.C(O)(=O)C.CS(C)=O>[CH3:19][C:20]1[S:29][C:28]2[NH:27][C:26]3[CH:30]=[CH:31][CH:32]=[CH:33][C:25]=3[N:24]=[C:23]([N:17]3[CH2:16][CH2:15][NH:14][C@@H:13]([CH2:12][CH2:11][C:1]4[C:10]5[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=5)[CH:4]=[CH:3][CH:2]=4)[CH2:18]3)[C:22]=2[CH:21]=1
Reactant: c1ccc2c(CC[C@H]3CNCCN3)cccc2c1
Reactant: Cc1cc2c(s1)Nc1ccccc1N=C2N
Solvent: CC(=O)O
Solvent: CCN(C(C)C)C(C)C
Solvent: Cc1ccccc1
Product: Cc1cc2c(s1)Nc1ccccc1N=C2N1CCN[C@@H](CCc2cccc3ccccc23)C1
Temperature: 105 °C
Reaction time: 48 h
Yield: 4.7 %

Procedure:
Combine (S)-2-(2-naphthalen-1-yl-ethyl)-piperazine (686 mg, 2.85 mmol), 2-methyl-4H-3-thia-4,9-diaza-benzo[f]azulen-10-ylamine (654 mg, 2.85 mmol), toluene (5.7 mL), DMSO (1.4 mL) and glacial acetic acid (0.5 mL). Add N-ethyldiisopropylamine (2.0 mL). Heat at 105° C. After 48 h, cool to ambient temperature and dilute with ethyl acetate and water. Extract with ethyl acetate. Wash the extracts with water and brine, dry over sodium sulfate, filter and concentrate the filtrate. Purify by silica gel chromatography using 2N ammonia in methanol-methylene chloride (0.5%–5%) as the eluent to give 183 mg. Purify again by radial silica gel chromatography using a 2 mm plate and 2N ammonia in methanol-methylene chloride (1%–2%) as the eluent to give 60 mg (5%) of the title compound: mass spectrum (ion spray): m/z=453 (M+1), 451 (M−1). Analysis calculated for C28H28N4S.0.2H2O: C, 73.71; H, 6.27; N, 12.28. Found: C, 73.37; H, 6.19; N, 12.00.
Reaction SMILES: [CH2:1]([NH:5][CH2:6][P:7]([OH:10])([OH:9])=[O:8])[C:2]([OH:4])=[O:3].[OH-].[K+:12]>O>[CH2:1]([NH:5][CH2:6][P:7]([O-:10])([OH:9])=[O:8])[C:2]([OH:4])=[O:3].[K+:12]
Reactant: O=C(O)CNCP(=O)(O)O
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: O=C(O)CNCP(=O)([O-])O

Procedure:
The procedure of Example 1 is followed using 486.19 g of glyphosate acid, 323.23 g of deionized water, and 190.58 g of KOH pellets. The resulting potassium glyphosate concentrate (1000 g) has 44.0% acid equivalents. The final pH of the concentrate, measured as a 10% solution in deionized water, is 4.5.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].S(=O)(=O)(O)O.[CH3:17]O>>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([CH:10]=1)[C:7]([O:9][CH3:17])=[O:8]
Reactant: Nc1ccc(O)c(C(=O)O)c1
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)c1cc(N)ccc1O
Temperature: 25 °C
Yield: 89 %

Procedure:
5-Amino-2-hydroxybenzoic acid (10 g, 65.3 mmol) was suspended in MeOH (150 ml), and aqueous 96% sulfuric acid (12 ml, 225 mmol) was added drop wise. The mixture was heated to reflux for 96 hours. After cooling to RT, the solvent was partially removed under vacuum; the remaining solution was basified with NaHCO3 5% and extracted with EtOAc. The organic layer was washed with brine and dried over Na2SO4. The solvent was evaporated under vacuum affording methyl 5-amino-2-hydroxybenzoate as a solid (9.68 g, 57.9 mmol, 89% yield, MS/EST+168.0 [MH]+).
Reaction SMILES: [CH:1]1[CH:6]=[C:5]2[C:7]([O:9][C:10]3([C:20]4[CH:21]=[CH:22][C:23]([O-:25])=[CH:24][C:19]=4[O:18][C:12]4[CH:13]=[C:14]([O-:17])[CH:15]=[CH:16][C:11]3=4)[C:4]2=[CH:3][CH:2]=1)=[O:8].[Na+].[Na+].COC=C.C1(=O)OC(=O)C=C1>>[CH:2]1[CH:1]=[CH:6][C:5]([C:7]([OH:9])=[O:8])=[C:4]([C:10]2[C:11]3[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][C:12]=3[O:18][C:19]3[C:20]=2[CH:21]=[CH:22][C:23]([CH:24]=3)=[O:25])[CH:3]=1
Reactant: O=C1OC2(c3ccc([O-])cc3Oc3cc([O-])ccc32)c2ccccc21
Agent: C=COC
Agent: O=C1C=CC(=O)O1
Agent: [Na+]
Product: O=C(O)c1ccccc1-c1c2ccc(=O)cc-2oc2cc(O)ccc12

Procedure:
In order to determine the temperature stability and release profile of the nonaqueous drug delivery vehicle suspensions of the present invention microparticulates containing 5% sodium fluorescein were prepared utilizing poly(methylvinylether/maleic anhydride) as the polymer matrix utilizing the manufacturing technique of Example 1 and were suspended in PFD as a 2% w/v suspension utilizing the technique of Example 4. This nonaqueous drug delivery vehicle suspension was divided in half and equal portions were stored at 23° C. and at 45° C. for thirty days. Samples were taken of each portion during the thirty day test period and fluorescein release profiles were obtained as is known in the art. More specifically, the dissolution tests were performed as follows. 500 ml of 7.4 pH phosphate buffer (0.05M) was added to the kettles in the standard USP dissolution apparatus set at 37° C. 10 ml of the 2% w/v suspension was slowly added to the dissolution medium and the propeller speed was set to 50 rpm. Over a seven hour time period, samples were taken from the dissolution medium and immediately centrifuged. The supernatant containing the released fluorescein was assayed for fluorescein content by UV spectrophotometry. Release profiles for the 23° C. and 45° C. samples are given in FIGS. 1 and 2. The control was freshly prepared microparticulates.
Reaction SMILES: C[O-].[Na+].[C:4]([O:11][CH3:12])(=[O:10])[CH2:5][C:6]([O:8][CH3:9])=[O:7].F[C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:15]=1[N+:21]([O-:23])=[O:22].Cl>C1(C)C=CC=CC=1.C1CCCCC1.CS(C)=O>[F:20][C:18]1[CH:17]=[CH:16][C:15]([N+:21]([O-:23])=[O:22])=[C:14]([CH:5]([C:4]([O:11][CH3:12])=[O:10])[C:6]([O:8][CH3:9])=[O:7])[CH:19]=1
Reactant: COC(=O)CC(=O)OC
Reactant: O=[N+]([O-])c1ccc(F)cc1F
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CS(C)=O
Solvent: C1CCCCC1
Solvent: Cc1ccccc1
Product: COC(=O)C(C(=O)OC)c1cc(F)ccc1[N+](=O)[O-]
Temperature: 25 °C
Yield: 65.8 %

Procedure:
In a flask made of glass equipped with a stirrer, a thermometer, a distillation device and a dropping funnel and having an inner volume of 200 ml were charged 3.40 g (62.9 mmol) of sodium methoxide and 30 ml dimethyl sulfoxide under argon atmosphere, and then, while stirring at room temperature, 8.48 g (62.9 mmol) of dimethyl malonate with a purity of 98% was gradually added dropwise over 5 minutes. Moreover, 10 ml of cyclohexane was added to the mixture, and after raising the temperature to 100 to 105° C., the formed methanol was subjected to azeotropic distillation (removed by distillation) with cyclohexane. After this operation (removal of methanol by distillation) was repeated twice, the reaction mixture was cooled to 70° C., and 5.10 g (31.4 mmol) of 2,4-difluoronitrobenzene with a purity of 98% was gradually added dropwise over 10 minutes, and the resulting mixture was reacted at 70 to 80° C. for one hour. After completion of the reaction, the mixture was cooled to room temperature, 100 ml of toluene was added to the mixture and 5.25 ml (31.4 mmol) of 6 mol/l hydrochloric acid was gradually added dropwise while stirring. Then, the organic layer was separated, and the resulting mixture was washed successively with 50 ml of water and 50 ml of a saturated saline solution in this order, and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography (filler:Daisogel 1002W, eluent:hexane:ethyl acetate=9:1 (volume ratio)) to obtain 5.60 g of dimethyl 2-(5-fluoro-2-nitrophenyl)malonate (isolation yield: 64%) as white crystals with a purity of 98% (areal percentage by high performance liquid chromatography).
Reaction SMILES: [CH2:1]([NH:13][C:14](=[O:18])[C@H:15]([CH3:17])[NH2:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[OH-].[Na+].[CH:21](=O)[C:22]1[C:23](=[CH:25][CH:26]=[CH:27][CH:28]=1)[OH:24].[BH4-].[Na+]>CO>[CH2:1]([NH:13][C:14](=[O:18])[C@H:15]([CH3:17])[NH:16][CH2:21][C:22]1[CH:28]=[CH:27][CH:26]=[CH:25][C:23]=1[OH:24])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCCNC(=O)[C@H](C)N
Reactant: O=Cc1ccccc1O
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCCCCCCCCCCCNC(=O)[C@H](C)NCc1ccccc1O
Reaction time: 1 h

Procedure:
L-alanine laurylamide (2.5 g) and 1 g of sodium hydroxide were dissolved in 20 ml of methanol, and 1.0 ml of salicylaldehyde and 0.1 g of sodium borohydride were added thereto in this order. After the mixture was stirred for 1 hour, 1.0 ml of salicylaldehyde and 0.1 g of sodium borohydride were added thereto again in this order. The mixture was stirred overnight at room temperature, and the insoluble matter was then separated through filtration. The filtrate was adjusted to a pH of 7 with hydrochloric acid, and concentrated under reduced pressure. The resulting oil was dissolved in diethyl ether, washed with water, and then dried over with magnesium sulfate. After the drying agent was separated through filtration, the filtrate was concentrated under reduced pressure to give 3 g of N-(2-hydroxybenzyl)-L-alanine laurylamide.
Reaction SMILES: [S:1]1[CH:5]=[C:4]([CH2:6][C:7](O)=[O:8])[C:3]2[CH:10]=[CH:11][CH:12]=[CH:13][C:2]1=2.[Li].C(O)C>O1CCCC1>[S:1]1[CH:5]=[C:4]([CH2:6][CH2:7][OH:8])[C:3]2[CH:10]=[CH:11][CH:12]=[CH:13][C:2]1=2
Reactant: O=C(O)Cc1csc2ccccc12
Agent: [Li]
Solvent: CCO
Solvent: C1CCOC1
Product: OCCc1csc2ccccc12
Temperature: 60 °C
Reaction time: 1 h

Procedure:
A solution of benzo[b]thiophen-3-yl-acetic acid (6.0 g, 31.2 mmol) in 40 ml of tetrahydrofuran was added dropwise at RT to a suspension of lithium alanate (1.54 g, 41 mmol) in 35 ml of tetrahydrofuran. The mixture was stirred for 60 minutes at 60° C., and then excess alanate was hydrolysed with ethanol. The mixture was suction-filtered over Kieselguhr and the solvent was removed in vacuo. The product was obtained in the form of a yellowish oil in a yield of 5.1 g (92%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([F:11])[C:9]=1F)[CH:5]=[O:6].[CH3:12][S-:13].[Na+].O>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([F:11])[C:9]=1[S:13][CH3:12])[CH:5]=[O:6]
Reactant: C[S-]
Reactant: O=Cc1cc(F)c(F)c(F)c1
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CSc1c(F)cc(C=O)cc1F
Temperature: 25 °C
Reaction time: 18 h
Yield: 62.5 %

Procedure:
To a solution of 3,4,5-trifluorobenzaldehyde (30.0 g, 0.187 mol) in anhydrous THF (400 mL) cooled in a cold water bath was added sodium thiomethoxide (14.4 g, 0.20 mol) in portions over 30 minutes. The mixture was stirred at room temperature for 18 hours, then poured into water and extracted with dichloromethane (1×500 mL, 2×200 mL). The combined extracts were washed with water, dried using magnesium sulfate, and concentrated. Purification of the product by silica gel chromatography using 2% dichloromethane/5% ethyl acetate in hexanes gave the 3,5-difluoro-4-(methylthio)-benzaldehyde as a clear colorless liquid (22.0 g, 62%). 1H NMR (CDCl3/400 MHz) 9.86 (t, J=1.5, 1H), 7.34-7.39 (m, 2H), 2.55 (s, 3H). HRMS m/z 188.0099 (M+, calcd 188.0107).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11](=[O:13])[CH3:12])=[CH:6][CH:5]=1)([O-])=O>CO.[Pd]>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([CH2:10][C:11](=[O:13])[CH3:12])=[CH:8][CH:9]=1
Reactant: CC(=O)Cc1ccc([N+](=O)[O-])cc1
Agent: [Pd]
Solvent: CO
Product: CC(=O)Cc1ccc(N)cc1
Temperature: 25 °C
Reaction time: 10 h
Yield: 48 %

Procedure:
1-(4-nitro-phenyl)-propan-2-one (150 mg) was dissolved in methanol (5 ml) and then Pd/C (50 mg) was added. The resulting reaction mixture was stirred for 10 hr at room temperature under hydrogen pressure. The reaction mixture was filtered over celite and the filtrate evaporated. Purification by column chromatography over silica gel using ethyl acetate and hexane (1:9) as eluent gave 1-(4-amino-phenyl)-propan-2-one (60 mg, 48%).
Reaction SMILES: [C:1]1(O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[NH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[CH:14]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>>[CH3:19][C:15]1[CH:14]=[C:13]([NH:12][C:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:4]=[CH:3][CH:2]=2)[CH:18]=[CH:17][CH:16]=1
Reactant: Cc1cccc(N)c1
Reactant: Oc1cccc2ccccc12
Agent: c1ccc(OP(Oc2ccccc2)Oc2ccccc2)cc1
Product: Cc1cccc(Nc2cccc3ccccc23)c1
Yield: 94 %

Procedure:
216 parts of α-naphthol, 214 parts of m-toluidine and 10 parts of triphenyl phosphite are mixed. The reaction is carried out analogously to Example 7. After removing 27 parts of water, the reaction has ended. After distilling off excess m-toluidine, 330 parts of N-m-tolyl-α-naphthylamine, corresponding to a yield of 94% of theory, are obtained at a boiling point of 203° - 206° C/5 mm Hg.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:16]=[CH:15][C:6]2[O:7][C:8]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:9][C:5]=2[CH:4]=1.[C-:17]#[N:18].[Na+]>CN(C)C=O>[C:17]([CH2:2][C:3]1[CH:16]=[CH:15][C:6]2[O:7][C:8]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:9][C:5]=2[CH:4]=1)#[N:18]
Reactant: [C-]#N
Reactant: CCOC(=O)c1cc2cc(CCl)ccc2o1
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1cc2cc(CC#N)ccc2o1
Yield: 90 %

Procedure:
The starting material can be prepared as follows: By the reaction of ethyl 5-chloromethylbenzo[b]furan-2-carboxylate (Chem. Abstr., 1959, 3185d) with excess sodium cyanide in dimethylformamide there is obtained, in a yield of 90% of theory, ethyl 5-cyanomethylbenzo[b]furan-2-carboxylate (m.p. 74°-76° C. after recrystallisation from ethyl acetate) which is hydrogenated in the presence of platinum oxide to give ethyl 5-(2-aminoethyl)-benzo[b]furan-2-carboxylate. From an ethanolic solution thereof, with an ethereal solution of hydrogen chloride there can be precipitated out the hydrochloride; m.p. 188°-190° C.; yield 64% of theory.
Reaction SMILES: C1(C)C=CC=CC=1.C1COCC1.[B:13](OC(C)C)([O:18]C(C)C)[O:14]C(C)C.[F:26][C:27]1[CH:28]=[C:29]([CH3:34])[CH:30]=[CH:31][C:32]=1Br>CCCCCC.C(#N)C>[F:26][C:27]1[CH:28]=[C:29]([CH3:34])[CH:30]=[CH:31][C:32]=1[B:13]([OH:18])[OH:14]
Reactant: Cc1ccc(Br)c(F)c1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Solvent: CCCCCC
Product: Cc1ccc(B(O)O)c(F)c1
Temperature: -40 °C

Procedure:
To a mixture of toluene (160 ml) and THF (40 ml) are added triisopropyl borate (13.56 ml, 58.42 mmole) and 3-fluoro-4-bromotoluene (10.0 g, 48.69 mmole). The mixture is cooled down to −40° C. and n-Butylithium (2.5M in hexane) (23.4 ml, 58.42 mmole) is added slowly over 1 h and the mixture is stirred for an additional hour while the temperature is held at −40° C. The acetone/dry ice bath is removed and the reaction mixture is allowed to warm to −20° C. before a 2.5M HCl solution (20 ml) is added. When the mixture reached rt, the aqueous layer is extracted with EtOAc (3×50 ml), organic extracts are combined, dried over MgSO4 (anhydrous) and evaporated under reduced pressure to give a yellow solid, which is recrystalilsed from acetonitrile, affording the title product.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Cl:10])[CH:9]=1)[CH:5]=O.C(O)(=O)[CH2:12][C:13]([OH:15])=[O:14].N1CCCCC1>N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Cl:10])[CH:9]=1)[CH:5]=[CH:12][C:13]([OH:15])=[O:14]
Reactant: O=Cc1cc(Cl)cc(Cl)c1
Reactant: O=C(O)CC(=O)O
Solvent: C1CCNCC1
Solvent: c1ccncc1
Product: O=C(O)C=Cc1cc(Cl)cc(Cl)c1
Yield: 68.5 %

Procedure:
Reaction of 3,5-dichlorobenzaldehyde (26.9 g, 0.154 mole), malonic acid (24.1 g, 0.232 mole), pyridine (8 ml) and piperidine (0.4 ml) substantially as above yielded 22.9 g (69%) of 3,5-dichlorocinnamic acid as white needles: mp 169-170° (ethanol).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[C:6]([Cl:9])[C:7]=1[Cl:8].Br[C:14]([C:16]([F:19])([F:18])[F:17])=[CH2:15].C([O-])([O-])=O.[K+].[K+]>C1COCC1.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>[Cl:1][C:2]1[CH:3]=[C:4]([C:14]([C:16]([F:19])([F:18])[F:17])=[CH2:15])[CH:5]=[C:6]([Cl:9])[C:7]=1[Cl:8]
Reactant: OB(O)c1cc(Cl)c(Cl)c(Cl)c1
Reactant: C=C(Br)C(F)(F)F
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: C=C(c1cc(Cl)c(Cl)c(Cl)c1)C(F)(F)F
Temperature: 80 °C
Yield: 89.5 %

Procedure:
A mixture of 3,4,5-trichlorophenylboronic acid (3.376 g, 15 mmol), 2-bromo-3,3,3-trifluoroprop-1-ene (4.02 g, 23 mmol), K2CO3 (4.15 g, 30 mmol) and Pd(PPh3)2Cl2 (4.15 g, 30 mmol) in THF (16 mL) and H2O (8 mL) was heated at 80° C. in a sealed tube for 4 h. The mixture was cooled to rt and partitioned between EA (50 mL) and H2O (50 mL). The aqueous layer was extracted with EA (50 mL) and the combined organic layers were dried over anhydrous Na2SO4. The solvent was removed under reduced pressure and the crude product was purified by column chromatography on silica gel to give the crude desired product (3.7 g; 90% yield) as a pale yellow solid.
Reaction SMILES: CS(O[C:6]1[CH:11]=[CH:10][C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:8][C:7]=1[C:16]([CH3:19])([CH3:18])[CH3:17])(=O)=O.C([O-])=O.[NH4+].C([O-])(=O)C.[Li+].CO>[Pd].[C].O>[C:12]([C:9]1[CH:10]=[CH:11][CH:6]=[C:7]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH:8]=1)([CH3:15])([CH3:14])[CH3:13]
Reactant: CC(C)(C)c1ccc(OS(C)(=O)=O)c(C(C)(C)C)c1
Agent: [Pd]
Agent: CC(=O)[O-]
Agent: O=C[O-]
Solvent: CO
Solvent: O
Product: CC(C)(C)c1cccc(C(C)(C)C)c1
Yield: 76.4 %

Procedure:
In a nitrogen atmosphere under normal pressure, 2,4-di-tert-butylphenyl methanesulfonate (30 g, 0.11 mols), ammonium formate (8.0 g, 0.13 mols), lithium acetate (8.4 g, 0.13 mols) and methanol (45 g) were mixed at 25° C., and with stirring, 10 mass % Pd/carbon (50 mass % water-containing product) (1.2 g) (as metal palladium; 0.2 mass % relative to 2,4-di-tert-butylphenyl methanesulfonate) as supported by a carbon carrier having a specific surface area of 780 m2/g (by BET method) was put into it. With stirring, the reaction liquid was reacted at the same temperature for 4 hours. Water (10 mL) was added to the reaction liquid and Pd-carbon was separated through filtration, then heptane (30 g) was added to the filtrate. The organic layer obtained after extraction was concentrated under reduced pressure to give crude 1,3-di-tert-butylbenzene (16 g, yield 81% by mass). The result is shown in Table II-3.
Reaction SMILES: [CH3:1][C:2]1([CH3:17])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH:7]=[C:6]([C:14]([OH:16])=O)[CH:5]=[CH:4][C:3]1=2.[F:18][C:19]1[CH:25]=[CH:24][C:22]([NH2:23])=[CH:21][CH:20]=1>>[F:18][C:19]1[CH:25]=[CH:24][C:22]([NH:23][C:14]([C:6]2[CH:5]=[CH:4][C:3]3[C:2]([CH3:1])([CH3:17])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]=3[CH:7]=2)=[O:16])=[CH:21][CH:20]=1
Reactant: Nc1ccc(F)cc1
Reactant: CC1(C)CCC(C)(C)c2cc(C(=O)O)ccc21
Product: CC1(C)CCC(C)(C)c2cc(C(=O)Nc3ccc(F)cc3)ccc21
Yield: 60.7 %

Procedure:
In a manner analogous to Example 1, 2 g of 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalene-carboxylic acid and 1 g of 4-fluoroaniline were used to obtain 1.7 g of 4'-fluoro-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenecarboxanilide in colorless crystals. m.p. 163° C.-165° C. (from ethyl acetate/hexane).
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([C@H:14]1[C:19](=O)[NH:18][CH2:17][C:16](=O)[NH:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>O1CCCC1>[CH2:7]([C@H:14]1[CH2:19][NH:18][CH2:17][CH2:16][NH:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: O=C1CNC(=O)[C@H](Cc2ccccc2)N1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: c1ccc(C[C@H]2CNCCN2)cc1
Reaction time: 0.5 h

Procedure:
At ice-bath temperature, lithium aluminium hydride (1.6 g, 42.16 mmol) was added in portions to a stirring mixture of (S)-2-benzylpiperazine-3,6-dione (3.0 g, 14.70 mmol) (comm. avail.) and tetrahydrofuran (80 ml). After 30 min at ice-bath temperature, the mixture was refluxed for 4 h with stirring. The reaction was quenched by the portionwise addition of sodium sulfate decahydrate and some methanol until hydrogen evolution ceased. It was filtered and the solids were washed several times with dichloromethane. The combined filtrates were evaporated to leave a white solid.MS (m/z): 177.1 (M+H)+; C11H16N2 requir. 176.3.
Reaction SMILES: [C:1]([O:5][C:6](=[O:19])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-])=O)=[C:10]([O:17][CH3:18])[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[NH4+].[Cl-]>CO.[Zn]>[C:1]([O:5][C:6](=[O:19])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([NH2:14])=[C:10]([O:17][CH3:18])[CH:9]=1)([CH3:3])([CH3:4])[CH3:2]
Reactant: COc1cc(CC(=O)OC(C)(C)C)ccc1[N+](=O)[O-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: CO
Product: COc1cc(CC(=O)OC(C)(C)C)ccc1N
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 94.1 %

Procedure:
Step C A suspension of (3-methoxy-4-nitro-phenyl)-acetic acid tert-butyl ester (3 g, 11.2 mmol) in methanol (100 mL) was added an aqueous solution (50 mL) of NH4Cl (6 g, 112 mmol), followed by activated zinc (Aldrich, 7.3 g, 112 mmol). The reaction mixture was stirred at room temperature for 0.5 h. The mixture was filtered through a short pad of celite. The mixture was concentrated. The residue was partitioned between ethyl acetate and water. The organic layer was separated, and aqueous layer was extracted with ethyl acetate. The combined organic extract was washed with water, brine, dried over MgSO4, and concentrated to give (4-amino-3-methoxy-phenyl)-acetic acid tert-butyl ester as a brown oil (2.5 g, 94%).