Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CO[C:3](=[O:25])[C@@H:4]1[CH2:8][C@@H:7]([OH:9])[CH2:6][N:5]1[C:10](=[O:24])[C:11]1[CH:16]=[C:15]([O:17][CH3:18])[C:14](OC)=[CH:13][C:12]=1[N+:21]([O-])=O.C(Cl)(Cl)Cl.C[CH2:31][OH:32]>[Pd].Cl>[CH3:31][O:32][C:16]1[C:11]2[C:10](=[O:24])[N:5]3[CH2:6][C@H:7]([OH:9])[CH2:8][C@H:4]3[C:3](=[O:25])[NH:21][C:12]=2[CH:13]=[CH:14][C:15]=1[O:17][CH3:18]
Reactant: COC(=O)[C@@H]1C[C@@H](O)CN1C(=O)c1cc(OC)c(OC)cc1[N+](=O)[O-]
Reactant: CCO
Agent: [Pd]
Agent: Cl
Solvent: ClC(Cl)Cl
Product: COc1ccc2c(c1OC)C(=O)N1C[C@H](O)C[C@H]1C(=O)N2

Procedure:
10% Pd/C catalyst (3.3 g) was added to a solution of 169 (33.0 g, 93.1 mmol) in absolute EtOH (250 mL). The reaction mixture was hydrogenated under pressure using a Parr hydrogenator at 55 psi H2 for 18 h. The reaction mixture was filtered through celite, and the celite washed with hot MeOH, taking care not to allow the filter cake to dry out. Removal of excess solvent afforded the crude product (20.14 g). The crude product was allowed to stir in 1 N HCl (200 mL) and CHCl3 (200 mL) for 30 minutes. The organic layer was washed with 1 N HCl (100 mL) and the aqueous layers were combined and neutralised with saturated aqueous NaHCO3. On leaving the aqueous extract overnight, a fine white precipitate formed (170) which was collected by filtration and dried (7.81 g, 26.72 mol, 29%). 1H NMR (270 MHz, CDCl3) d 10.06 (s, 1H, NH), 7.61 (s, 1H, ArH), 7.36 (s, 1H, ArH), 4.49-4.41 (m, 1H, 2), 4.22-4.17 (m, 1H, 11a), 3.88 (s, 6H), 3.82-3.55 (m, 2H., 3), 3.20 (br s, 1H, OH), 2.87-2.77 (m, 1H, 1), 2.10-2.05 (m, 1H, 1); 13C NMR (CDCl3) d 170.2, 165.9, 152.0, 145.7, 130.7, 118.2, 111.9, 104.2, 68.1, 56.0, 55.6, 54.2, 34.6, 18.8.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([CH2:7][CH2:8][C:9]2[O:10][CH:11]=[CH:12][CH:13]=2)=[CH:3][CH:2]=1.[CH2:14](Br)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[BH4-].[Na+]>CN(C)C=O.C(O)C>[CH2:14]([N:1]1[CH2:6][CH:5]=[C:4]([CH2:7][CH2:8][C:9]2[O:10][CH:11]=[CH:12][CH:13]=2)[CH2:3][CH2:2]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: BrCc1ccccc1
Reactant: c1coc(CCc2ccncc2)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: CN(C)C=O
Product: C1=C(CCc2ccco2)CCN(Cc2ccccc2)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 74.2 %

Procedure:
A solution of 1-(pyridin-4-yl)-2-(furan-2-yl)ethane (2 g, 11.6 mmol) in anhydrous dimethylformamide (5 ml) was treated with benzyl bromide (1.5 ml, 12.7 mmol) and the reaction stirred at room temperature for one hour. The reaction was diluted with ethanol (50 ml), treated with sodium borohydride (0.55 g, 14.5 mmol) and heated at reflux for one hour. The solvent was evaporated and the residue partitioned between ethyl acetate and water. The organic was separated, dried (Na2SO4) and evaporated to give crude product as a yellow oil. This material was triturated with diethyl ether to afford the title compound (2.3 g, 68%) as a colourless solid; δH (DMSO-d6) 1.92-2.10 (2H, m, tetrahydropyridinyl CH2), 2.14-2.30 (2H, m, CH2), 2.36-2.50 (2H, m, CH2), 2.60-2.82 (2H, m, tetrahydropyridinyl CH2), 2.84-2.90 (2H, m, tetrahydropyridinyl CH2), 3.50 (2H, br s, PhCH2N), 5.32-5.44 (1H, m, tetrahydropyridinyl 5-H), 6.02-6.10 (1H, m, furanyl H), 6.30-6.36 (1H, m, furanyl H), 7.16-7.36 (5H, m, ArH), and 7.44-7.52 (1H, m, furanyl H); m/z (CI+, NH3) 268 (M+1)+.
Reaction SMILES: [CH2:1]1[C:10]2[C:5](=[C:6]([O:11][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][NH:2]1.CCN(CC)CC.[CH3:25][S:26](Cl)(=[O:28])=[O:27]>C(Cl)Cl>[CH3:25][S:26]([N:2]1[CH2:3][CH2:4][C:5]2[C:10](=[CH:9][CH:8]=[CH:7][C:6]=2[O:11][CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:1]1)(=[O:28])=[O:27]
Reactant: CCOC(=O)COc1cccc2c1CCNC2
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)COc1cccc2c1CCN(S(C)(=O)=O)C2
Temperature: 25 °C
Reaction time: 16 h
Yield: 77.8 %

Procedure:
To a solution of ethyl 2-((1,2,3,4-tetrahydroisoquinolin-5-yl)oxy)acetate (300 mg, 1.28 mmol) and Et3N (387 mg, 3.83 mmol) in DCM (25 mL) cooled in an ice-water bath was added MsCl (176.6 mg, 1.54 mmol) drop wise. The mixture was stirred at 25° C. for 16 h and then quenched with aq.NH4Cl. The mixture was extracted with ethyl acetate and the combined organic layers were concentrated under vacuum to give the crude product (312 mg, 78%) which was used to the next step without purification.
Reaction SMILES: [N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]([OH:9])[CH2:2]2.[H-].[Na+].[Br:12][C:13]1[CH:14]=[C:15]([N:19]=[C:20]=[O:21])[CH:16]=[CH:17][CH:18]=1>C1COCC1>[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]([O:9][C:20](=[O:21])[NH:19][C:15]1[CH:16]=[CH:17][CH:18]=[C:13]([Br:12])[CH:14]=1)[CH2:2]2
Reactant: OC1CN2CCC1CC2
Reactant: O=C=Nc1cccc(Br)c1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C(Nc1cccc(Br)c1)OC1CN2CCC1CC2
Reaction time: 0.25 h
Yield: 43.1 %

Procedure:
To a solution of quinuclidin-3-ol (635 mg, 5.00 mmol) in THF (15 mL) was added NaH [60% dispersion in mineral oil] (260 mg, 6.50 mmol) at room temperature. The mixture was stirred for 15 min and 3-bromophenyl isocyanate (990 mg, 5.00 mmol) was added under stirring. The resulting mixture was stirred at room temperature for 18 h, quenched with brine and extracted with EtOAc. The organic layers were combined, dried over Na2SO4 and concentrated. The crude product was purified by silica gel column chromatography (eluting with EtOAc/methanol 3:1) to give quinuclidin-3-yl3-bromophenylcarbamate as a white solid (0.70 g, 43%).
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]([CH:14]=[O:15])[O:12][CH:13]=2)O1.Cl[C:18]1[C:19]2[CH:26]=[CH:25][NH:24][C:20]=2[N:21]=[CH:22][N:23]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C>[N:21]1[C:20]2[NH:24][CH:25]=[CH:26][C:19]=2[C:18]([C:9]2[CH:10]=[C:11]([CH:14]=[O:15])[O:12][CH:13]=2)=[N:23][CH:22]=1
Reactant: Clc1ncnc2[nH]ccc12
Reactant: CC1(C)OB(c2coc(C=O)c2)OC1(C)C
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=Cc1cc(-c2ncnc3[nH]ccc23)co1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 87 %

Procedure:
1 g [4.5 mMols] of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)furan-2-carbaldehyde, 550 mg [3.6 mMols]-4-chloro-7H-pyrrolo[2,3-d]pyrimidine and 1.52 g [6.7 mMols] of tripotassium phosphate were placed in 20 mL DMF and 10 mL water and purged with nitrogen gas while stirring for 10 minutes at ambient temperature. To this stirring suspension, 400 mg, 0.45 mMols] of tetrakistriphenylphosphine palladium (0) was added in one portion, and reaction vessel was placed in a preheated bath at 110° C. The reaction was stirred and heated under a nitrogen atmosphere for 30 minutes (deemed complete by analytical liquid chromatography). The reaction mixture was cooled and suction filtered to remove the ligand present as a precipitate, which was washed with a little DMF/H2O 2:1. The combined filtrates were reduced in volume to one quarter of the original under reduced pressure and diluted slowly with water with stirring. The resulting fine precipitate was centrifuged down and the pellet was washed with more water, re-centrifuged and transferred to a RB with acetonitrile. This solvent was reduced to dryness under reduced pressure. The material, 670 mg (yield 87%) of a light beige powder was carried on without further purification. LC/ms m+1=214.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[CH3:5][C:6]1([CH3:13])[NH:10][C:9](=[O:11])[CH2:8][C:7]1=[O:12].C(N(CC)CC)C>C(Cl)Cl>[C:1]([O:12][C:7]1[C:6]([CH3:13])([CH3:5])[NH:10][C:9](=[O:11])[CH:8]=1)(=[O:3])[CH3:2]
Reactant: CC1(C)NC(=O)CC1=O
Reactant: CC(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)OC1=CC(=O)NC1(C)C
Reaction time: 24 h
Yield: 18.7 %

Procedure:
At 0 to 5° C., a solution of 4.08 g of acetyl chloride in 20 of methylene chloride is added dropwise to a solution of 6.36 g of 5,5-dimethylpyrrolidine-2,4-dione and 5.57 g of triethylamine in 50 ml of methylene chloride. The mixture is then left to reach room temperature over the course of approximately one hour and then stirred for a further 24 hours. The reaction mixture is then diluted with 50 ml of methylene chloride, and extracted by shaking twice with in each case 50 ml of water, twice with in each case 25 ml of 5% strength sodium hydroxide solution and once with 50 ml of saturated aqueous NaCl solution. Drying and concentration by evaporation gives 1.58 g of the title compound in a purity according to HPLC of 97%.
Reaction SMILES: [F:1][C:2]1[C:3](N)=[N:4][C:5](=[O:8])[NH:6][CH:7]=1.FC1N=C([Cl:17])C(F)=CN=1>O>[OH:8][C:5]1[N:4]=[C:3]([Cl:17])[C:2]([F:1])=[CH:7][N:6]=1
Reactant: Fc1ncc(F)c(Cl)n1
Reactant: Nc1nc(=O)[nH]cc1F
Solvent: O
Product: Oc1ncc(F)c(Cl)n1

Procedure:
A process has now been found for the preparation of 5-fluorocytosine, which is characterised in that 2,5-difluoro-4-chloropyrimidine is reacted with a proton acid in the presence of water to give 2-hydroxy-4-chloro-5-fluoropyrimidine, and this is reacted with ammonia to give 2-hydroxy-4-amino-5-fluoropyrimidine (=5-fluorocytosine).
Reaction SMILES: C[O:2][C:3](=[O:19])[CH2:4][CH2:5][NH:6][C:7]1[CH:8]=[C:9]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1.[OH-].[Li+]>O.O1CCCC1>[C:9]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=[C:7]([NH:6][CH2:5][CH2:4][C:3]([OH:19])=[O:2])[CH:8]=1
Reactant: COC(=O)CCNc1cccc(-c2ccccc2)c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: O=C(O)CCNc1cccc(-c2ccccc2)c1
Temperature: 25 °C
Reaction time: 5 h
Yield: 105.3 %

Procedure:
3-(Biphenyl-3-ylamino)-propionic acid methyl ester 1.6 g (6.3 mmol) was taken in 8 mL of water and 8 mL of tetrahydrofuran, to this solution was added 0.4 g (9.5 mmol) of lithium hydroxide, reaction stirred at room temperature for 5 hour. The solvent was removed from the mixture completely and 10 mL water was added and washed with ethyl acetate. The aqueous solution was acidified with 1 M HCl, and was extracted with ethyl acetate 3 times. Combined organic layer was washed with brine, dried over magnesium sulfate and concentrated under vaccum, yield to 1.6 g of acid used as crude for the next step.
Reaction SMILES: [H-].[Na+].COP([CH2:9][C:10](=[O:16])[CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])(=O)OC.[CH3:17][C:18]1[S:19][C:20]([CH:33]=O)=[C:21]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30])[N:22]=1.C(CCCCCCC1N=CSC=1/C=C/C(=O)CCCCC)(OC)=O>COCCOC.O>[CH3:17][C:18]1[S:19][C:20](/[CH:33]=[CH:9]/[C:10](=[O:16])[CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])=[C:21]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30])[N:22]=1
Reactant: COC(=O)CCCCCCc1nc(C)sc1C=O
Reactant: CCCCCC(=O)CP(=O)(OC)OC
Agent: CCCCCC(=O)/C=C/c1scnc1CCCCCCC(=O)OC
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: CCCCCC(=O)/C=C/c1sc(C)nc1CCCCCCC(=O)OC
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To a suspension of 0.45 g of sodium hydride in 5 ml of anhydrous 1,2-dimethoxy-ethane a solution of 4.12 g of 2-oxoheptylphosphonic acid dimethyl ester in 20 ml of 1,2-dimethoxy-ethane was added under stirring at room temperature. The reaction mixture was stirred for an hour, then a solution of 1 g of 2-methyl-4-(6-carbomethoxyhexyl)-thiazole-5-carbaldehyde (XIII, R1 = CH3) prepared according to point (e) of Example 2, in 10 ml of 1,2-dimethoxy-ethane was added dropwise, and stirring was continued for 5 hours. After adding dropwise 30 ml of water under ice-cooling to the reaction mixture, it was extracted with 3 × 20 ml of diethyl ether. The extract was dried on over sodium sulphate and evaporated in vacuo. The evaporation residue was purified by preparative thin layer chromatography, using a silica gel layer as adsorbent and a mixture of 40 % ethyl acetate and 60 % n-heptane as running solvent. The yield was 0.81 g of 2-methyl-4-(6-carbomethoxyhexyl)-5-(3-keto-1-trans-octenyl)-thiazole (Ia, R1 = CH3) of chromatographic purity.
Reaction SMILES: [C:1]([C:5]1(C(OCC)=O)[O:9][NH:8][CH:7]=[CH:6]1)([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].O.[O:18]1CCC[CH2:19]1>C(O)C>[C:1]([C:5]1[O:9][N:8]=[C:7]([CH2:19][OH:18])[CH:6]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CCOC(=O)C1(C(C)(C)C)C=CNO1
Reactant: C1CCOC1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CC(C)(C)c1cc(CO)no1
Temperature: 25 °C
Reaction time: 10 h

Procedure:
1.83 g of ethyl 5-t-butyl-isoxazole-5-carboxylate was dissolved in 18 ml of tetrahydrofuran, and 0.70 g of sodium borohydride in 10 ml of ethanol was then added. The mixture was stirred at room temperature for 10 hours. After 5 ml of water was added, the reaction mixture was concentrated to 5 ml under reduced pressure. The concentrated solution was extracted with methyl-t-butyl ether. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure to obtain 0.62 g of (5-t-butyl-isoxazol-3-yl)methanol.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[NH:10][C:9](=O)[CH:8]=[CH:7]2.P(Cl)(Cl)([Cl:15])=O>>[Cl:15][C:9]1[CH:8]=[CH:7][C:6]2[C:11](=[C:2]([F:1])[CH:3]=[CH:4][CH:5]=2)[N:10]=1
Reactant: O=c1ccc2cccc(F)c2[nH]1
Reactant: O=P(Cl)(Cl)Cl
Product: Fc1cccc2ccc(Cl)nc12
Temperature: 125 °C
Yield: 73.8 %

Procedure:
8-Fluoroquinolin-2(1H)-one (26.0 g, 159 mmol) was slurried with phosphoryl trichloride (163 ml, 1.73 mol, 11 eq) and heated to 125° C. for 2 h. The reaction was cooled to rt and poured onto 1.2 L of ice water with vigorous stirring. When the mixture had cooled to rt, the orange solid was filtered and washed with water and dried under vacuum overnight to afford 27 g of crude material. The crude material was recrystallized from hexanes by dissolving in ˜700 mL of hexanes at reflux and decanting away from residual tar. The hexane solution was cooled to 0° C. and the precipitate 2-chloro-8-fluoroquinoline was filtered. The mother liquor was concentrated in vacuo and recrystallized from hexanes to obtain a second crop of 2-chloro-8-fluoroquinoline (21.3 g, 74% total yield).
Reaction SMILES: Cl[C:2]1[C:7]([CH3:8])=[CH:6][N:5]=[C:4]([CH3:9])[C:3]=1[CH3:10].[CH3:11][O-:12].[Na+].CS(C)=O>O>[CH3:11][O:12][C:2]1[C:7]([CH3:8])=[CH:6][N:5]=[C:4]([CH3:9])[C:3]=1[CH3:10]
Reactant: C[O-]
Reactant: Cc1cnc(C)c(C)c1Cl
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: COc1c(C)cnc(C)c1C
Reaction time: 8 h

Procedure:
60 g (0.39 mol) 4-chloro-2,3,5-trimethylpyridine and 21.7 g (0.40 mol) sodium methoxide and 180 ml dry dimethylsulfoxide was heated with stirring to 55°-60° C. for 8 hrs. The reaction mixture was diluted with 600 ml water and extracted with 3x100 ml toluene and the organic layer washed with 2x50 ml water. The organic phase was added to 200 ml water and pH adjusted to 4.1 with stirring. This process was repeated twice with 200 ml and 100 ml of water. The organic layer contained almost pure starting material. The combined water phase was made alkaline and extracted with 2×150 ml methylene chloride. Evaporation of solvent gave 40.7 g of almost pure 4-methoxy-2,3,5-trimethylpyridine. NMR: 2×3H, 2,2: 3H, 2,45(s); 3H, 3,75(s); 1H, 8,2(s). (CDCl3)
Reaction SMILES: C(OC(N1CCN(C2N=CC(C3C=CC(F)=CC=3)=CN=2)CC1)=O)(C)(C)C.[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][N:37]([C:40]2[N:45]=[CH:44][C:43](Br)=[CH:42][N:41]=2)[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28].[Cl:47][C:48]1[CH:49]=[C:50](B(O)O)[CH:51]=[CH:52][C:53]=1[Cl:54]>>[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][N:37]([C:40]2[N:45]=[CH:44][C:43]([C:51]3[CH:50]=[CH:49][C:48]([Cl:47])=[C:53]([Cl:54])[CH:52]=3)=[CH:42][N:41]=2)[CH2:36][CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28]
Reactant: OB(O)c1ccc(Cl)c(Cl)c1
Reactant: CC(C)(C)OC(=O)N1CCN(c2ncc(Br)cn2)CC1
Agent: CC(C)(C)OC(=O)N1CCN(c2ncc(-c3ccc(F)cc3)cn2)CC1
Product: CC(C)(C)OC(=O)N1CCN(c2ncc(-c3ccc(Cl)c(Cl)c3)cn2)CC1
Yield: 78 %

Procedure:
Prepared according to the method for the preparation of 4-[5-(4-fluorophenyl)pyrimidin-2-yl]piperazine-1-carboxylic acid tert-butyl ester, from 4-(5-bromopyrimidin-2-yl)piperazine-1-carboxylic acid tert-butyl ester (1.00 g) and 3,4-dichlorobenzeneboronic acid (0.61 g), to yield the title compound as a white solid (0.93 g, 78%).
Reaction SMILES: [CH:1]#[CH:2].[C:3]1(=[O:10])[NH:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1>>[CH:1]([N:9]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][C:3]1=[O:10])=[CH2:2]
Reactant: O=C1CCCCCN1
Reactant: C#C
Product: C=CN1CCCCCC1=O
Yield: 77.9 %

Procedure:
Example 1 was carried out without addition of a cocatalyst. The amount of ethyne taken up was 0.69 mol per mole of ε-caprolactam. The distillative workup yielded N-vinyl-ε-caprolactam in a yield of 77.9%. A viscid distillation residue was obtained.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.ClC1C(Cl)=C(S(N2CCC(O)CC2)(=O)=O)C=CC=1N[C:26](=[O:34])[C@:27]([OH:33])([CH3:32])[C:28]([F:31])([F:30])[F:29].[NH:35]([S:42]([C:45]1[C:51]([O:52][CH3:53])=[CH:50][C:48]([NH2:49])=[C:47]([O:54][CH3:55])[CH:46]=1)(=[O:44])=[O:43])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C(C1C=CC=C(C(C)(C)C)N=1)(C)(C)C>C(Cl)Cl.CN(C=O)C>[NH:35]([S:42]([C:45]1[C:51]([O:52][CH3:53])=[CH:50][C:48]([NH:49][C:26](=[O:34])[C@:27]([OH:33])([CH3:32])[C:28]([F:31])([F:30])[F:29])=[C:47]([O:54][CH3:55])[CH:46]=1)(=[O:44])=[O:43])[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1
Reactant: C[C@@](O)(C(=O)Nc1ccc(S(=O)(=O)N2CCC(O)CC2)c(Cl)c1Cl)C(F)(F)F
Reactant: COc1cc(S(=O)(=O)Nc2ccccc2)c(OC)cc1N
Agent: CC(C)(C)c1cccc(C(C)(C)C)n1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: COc1cc(S(=O)(=O)Nc2ccccc2)c(OC)cc1NC(=O)[C@@](C)(O)C(F)(F)F
Temperature: 25 °C
Reaction time: 8 h
Yield: 43.1 %

Procedure:
Oxalyl chloride (0.13 ml, 1.5 mmol) was added to a stirred suspension of (R)-(+)-2-hydroxy-2-methyl-3,3,3-trifluoropropanoic acid (0.154 g, 0.97 mmol) (Method 3) in DCM (10 ml) containing DMF (1 drop). The mixture was stirred at ambient temperature overnight, then 4-[anilinosulphonyl]-2,5-dimethoxyaniline (200 mg, 0.65 mmol)† and 2,6-di-t-butylpyridine (0.14 ml, 0.66 mmol) was added and the resulting mixture stirred a further 2 hours at room temperature. Dichloromethane (25 ml) was added and the mixture was washed with water (2×50 ml) and brine then dried. Volatile material was removed by evaporation and the residue was purified by chromatography on a silica gel Mega Bond Elut column eluting with 50% EtOAc/iso-hexane to give the title compound as a solid (0.125 g, 0.28 mmol); M.p: 194-195° C., NMR: 1.7 (s, 3H), 3.8 (s, 3H), 4.1 (s, 3H), 6.9 (s, 1H), 7.05 (m, 3H), 7.2 (m, 3H), 8.3 (s, 1H), 9.1 (brs, 1H); m/z 447.
Reaction SMILES: [C:1](O)(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]([OH:11])=[O:10].[C:14](O)(=O)[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]>>[C:9]([OH:11])(=[O:10])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]/[CH:1]=[CH:14]\[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: O=C(O)CCCCCCCC(=O)O
Reactant: CCCCCCCCC(=O)O
Product: CCCCCCCC/C=C\CCCCCCCC(=O)O

Procedure:
A process for the production of purified azelaic acid by working up a reaction mixture containing C1-18 monocarboxylic acids, comprising pelargonic acid, and C4-16 dicarboxylic acids, comprising azelaic acid, obtained from the ozonolysis of oleic acid or a starting mixture containing oleic acid, all but <2% by weight of the monocarboxylic acids and part of the dicarboxylic acids with a chain length of <C9 and >C9 being separated off to obtain a prepurified product containing more than 75% by weight of oleic acid and the prepurified product being concentrated to more than 90% by weight of oleic acid in several process steps of which the last is an overhead distillation step, which comprises: (1), removing the dicarboxylic acids with chain lengths of <C9, present in the prepurified product, as an overhead product by a first fractional distillation; (2), reacting a bottom product from the first distillation with water to split carboxylic anhydrides present in the bottom product to form a reaction mixture and, (3), distilling the reaction mixture to recover as an overhead product the purified azelaic acid, the third process step (3) being carried out after or at the same time as the second process step (2).
Reaction SMILES: [O:1]=[C:2]1[N:7]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[C:6]2[CH2:18][CH2:19][C:20](=[O:21])[C:5]=2[CH:4]([C:22]2[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=2)[NH:3]1.C([N-]C(C)C)(C)C.[Li+].Br[CH2:39][C:40]([O:42][CH3:43])=[O:41].O>C(#N)C>[C:26]([C:25]1[CH:24]=[CH:23][C:22]([CH:4]2[N:3]([CH2:39][C:40]([O:42][CH3:43])=[O:41])[C:2](=[O:1])[N:7]([C:8]3[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:15])([F:16])[F:17])[CH:9]=3)[C:6]3[CH2:18][CH2:19][C:20](=[O:21])[C:5]2=3)=[CH:29][CH:28]=1)#[N:27]
Reactant: N#Cc1ccc(C2NC(=O)N(c3cccc(C(F)(F)F)c3)C3=C2C(=O)CC3)cc1
Reactant: COC(=O)CBr
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: O
Solvent: CC#N
Product: COC(=O)CN1C(=O)N(c2cccc(C(F)(F)F)c2)C2=C(C(=O)CC2)C1c1ccc(C#N)cc1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
A solution of 4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]pyrimidin-4-yl)benzonitrile (example 1, 3.00 g, 7.55 mmol) in dry acetonitrile (45 mL) is cooled in an ice bath and treated dropwise with lithium diisopropylamide (2 M in THF, 7.55 mL, 15.1 mmol), while the temperature is kept below 5° C. Methyl 2-bromoacetate (2.31 g, 15.1 mmol) is added and the mixture is stirred for 1.5 h. The mixture is then warmed to room temperature and stirred at room temperature over night. Water (0.5 mL) is added, the mixture is concentrated, and the residue is purified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 2.64 g; ESI mass spectrum [M+H]+=470; Retention time HPLC: 1.65 min (W018_801).
Reaction SMILES: [CH2:1]([Cl:4])[CH:2]=[CH2:3].[SiH:5]([CH2:10][CH3:11])([CH2:8][CH3:9])[CH2:6][CH3:7].[SiH](Cl)(Cl)Cl>>[Si:5]([CH2:3][CH2:2][CH2:1][Cl:4])([CH2:10][CH3:11])([CH2:8][CH3:9])[CH2:6][CH3:7]
Reactant: CC[SiH](CC)CC
Reactant: C=CCCl
Agent: Cl[SiH](Cl)Cl
Product: CC[Si](CC)(CC)CCCCl
Temperature: 44 °C
Yield: 40.4 %

Procedure:
In a 50 ml apparatus, there were combined 7.7 g (0.1 mol) of allyl chloride and 0.05 ml of Pt catalyst solution. the mixture was heated to 44° C. and addition of a mixture of 11.6 g (0.1 mol) of Et3SiH and 1.4 g (0.01 mol) of Cl3SiH begun. Reaction was heated up to 54.5° C. during addition (30 min). There was a violent exothermic reaction from 62° C. to 110° C. 16 min later. Vacuum distillation yielded 7.79 g (40.5%) of Et3SiCH2CH2CH2Cl, with a Et3SiCH2CH2CH2Cl/Et3SiCl selectivity ratio of 1.23. This example and the previous one show that the preferred sequence of combination of reactants for most effective Cl3SiH promotion of the reaction of Et3SiH with allyl chloride is that of Example 24.
Reaction SMILES: [NH2:1][CH:2]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([O:18][CH3:19])[CH:12]=1)[C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[C:20](Cl)(=[O:29])[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C(Cl)Cl>[CH2:22]([O:21][C:20]([NH:1][CH:2]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([O:18][CH3:19])[CH:12]=1)[C:3]([O:5][C:6]([CH3:7])([CH3:9])[CH3:8])=[O:4])=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: COc1cc(CC(N)C(=O)OC(C)(C)C)ccc1O
Reactant: O=C(Cl)OCc1ccccc1
Solvent: ClCCl
Product: COc1cc(CC(NC(=O)OCc2ccccc2)C(=O)OC(C)(C)C)ccc1O
Reaction time: 0.17 h
Yield: 59 %

Procedure:
Prepared using General Procedure 2: To a stirred solution of tert-butyl 2-amino-3-(4-hydroxy-3-methoxyphenyl)propanoate INT-1 (5.29 g, 19.8 mmol) and TEA (4.29 mL, 29.7 mmol) in DCM (50 mL) at 0° C. was treated with benzyl carbonochloridate (3.00 mL, 21.1 mmol) dropwise over 5 min. After stirring for 10 min, the mixture was washed with 1M HCl (150 mL), dried over MgSO4, and concentrated. The residue was taken up in MeOH (20 mL) and treated with 2 N NaOH (5 mL). After 10 min, the mixture was acidified and the product was purified by chromatography (EA/hexanes) to afford 4.7 g (59%) of tert-butyl 2-(((benzyloxy)carbonyl)amino)-3-(4-hydroxy-3-methoxyphenyl)propanoate INT-2. LCMS-ESI (m/z) calculated for C22H27NO6: 401. Found 424 [M+Na]+, tR=2.47 min (Method 6).