Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([O:21][CH3:22])[C:18]=1[O:19][CH3:20])[CH:5]=[C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:8][C:7]1=[O:15].C(=O)([O-])[O-].[Na+].[Na+].[CH2:29]([O:31][C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1)[CH3:30].O>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:29]([O:31][C:32]1[CH:37]=[C:36]([C:3]2[CH:2]=[C:18]([O:19][CH3:20])[C:17]([O:21][CH3:22])=[CH:16][C:4]=2[CH:5]=[C:6]2[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[NH:8][C:7]2=[O:15])[CH:35]=[CH:34][CH:33]=1)[CH3:30]
Reactant: CCOc1cccc(B(O)O)c1
Reactant: COc1cc(C=C2C(=O)Nc3ccccc32)cc(Br)c1OC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCO
Solvent: O
Product: CCOc1cccc(-c2cc(OC)c(OC)cc2C=C2C(=O)Nc3ccccc32)c1
Reaction time: 12 h
Yield: 62.3 %

Procedure:
Tetrakis(triphenylphosphine)palladium(0) (0.02 g, 0.02 mmol) was added to a solution of 3-(3-bromo-4,5-dimethoxybenzylidene)-1,3-dihydroindol-2-one (0.2 g, 0.56 mmol) in toluene (1 ml) and ethanol (1 ml), followed by addition of 2M aqueous sodium carbonate (1 ml, 2 mmol). To this mixture was added 3-ethoxyphenylboronic acid (0.1 g, 0.62 mmol) and the mixture was held at 100° C. in a sealed tube for 12 hours. The reaction mixture was then added to water (40 ml) and extracted with ethyl acetate (2×75 ml) The combined organic layers were washed with saturated aqueous sodium bicarbonate (50 ml) and brine (50 ml), dried over magnesium sulfate and concentrated. The resulting solid was triturated with methylene chloride/hexanes to afford 0.14 g (64%) of 3-(3′-ethoxy-4,5-dimethoxybiphenyl-2-ylmethylene)-1,3-dihydroindol-2-one as a yellow/orange solid.
Reaction SMILES: Cl.[CH:2]1[C:10]2[N:9]3[C:11]([C@@H:14]4[C@H:18]([CH3:19])[CH2:17][C@H:16]([NH2:20])[CH2:15]4)=[CH:12][N:13]=[C:8]3[CH:7]=[N:6][C:5]=2[NH:4][CH:3]=1.O.C(=O)([O-])[O-].[K+].[K+].[F:28][C:29]([F:37])([F:36])[CH2:30][CH2:31][S:32](Cl)(=[O:34])=[O:33]>C1COCC1>[CH:2]1[C:10]2[N:9]3[C:11]([C@@H:14]4[C@H:18]([CH3:19])[CH2:17][C@H:16]([NH:20][S:32]([CH2:31][CH2:30][C:29]([F:37])([F:36])[F:28])(=[O:34])=[O:33])[CH2:15]4)=[CH:12][N:13]=[C:8]3[CH:7]=[N:6][C:5]=2[NH:4][CH:3]=1
Reactant: O=S(=O)(Cl)CCC(F)(F)F
Reactant: C[C@@H]1C[C@H](N)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: C[C@@H]1C[C@H](NS(=O)(=O)CCC(F)(F)F)C[C@@H]1c1cnc2cnc3[nH]ccc3n12
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 70.7 %

Procedure:
To a 2 L flask (1S,3S,4R)-3-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-4-methylcyclopentanamine hydrochloride (248.0 g, 733 mmol), water (1240 ml), THF (124 ml) and activated carbon (24.12 g) was added and stirred for about 10 min. The resulting mixture was filtered through celite rinsing with a mixture of water (100 mL) and THF (24 mL). Potassium carbonate (668 g, 4836 mmol) and THF (1736 ml) were added and a solution of 3,3,3-trifluoropropane-1-sulfonyl chloride (315 g, 1524 mmol, Matrix) in THF (620 ml) was added over about 1 hr. After cooling to ambient temperature the layers were separated and the aqueous layer extracted with THF (500 mL). The combined organic layers were washed with aqueous ammonium chloride (3×100 mL) and concentrated to approximately 1 L. Water (1770 mL) was added slowly at about 50° C. and the slurry cooled to about 23° C. The solids were collected by filtration, washed with 35% THF in water (750 mL) and dried in a vacuum oven. The crude material was dissolved in MeOH (4.5 L) and treated with activated carbon (28.3 g). After filtering through celite and rinsing with MeOH (500 mL), the solution was concentrated under reduced pressure to approximately 1 L and water (800 mL) was added slowly at about 50° C. then cooled to 35° C. when additional water (360 mL) was added. The product was collected by filtration, washed with 1:1 MeOH:water (2×350 mL) and dried in a vacuum oven to afford N-((1S,3S,4R)-3-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-4-methylcyclopentyl)-3,3,3-trifluoropropane-1-sulfonamide (215.3 g, 71%) as a white crystalline solid (m.p. 225° C.). 1H NMR (400 MHz, DMSO) δ 11.99 (bs, 1H), 8.30 (s, 1H), 7.40 (bs, 1H), 7.38 (s, 1H), 7.27-7.07 (m, 1H), 6.62 (d, J=3.4 Hz, 1H), 3.75 (dt, J=10.1, 7.8 Hz, 1H), 3.70-3.55 (m, 1H), 3.15-3.02 (m, 2H), 2.61-2.40 (m, 2H), 2.40-2.29 (m, 1H), 2.23 (dd, J=13.3, 6.9 Hz, 1H), 2.16-2.03 (m, 1H), 1.94-1.77 (m, 1H), 1.20-0.99 (m, 1H), 0.17 (d, J=7.0 Hz, 3H).
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:23][O:24][CH3:25])[C:8]([NH:10][CH:11]2[C:21](=[O:22])[N:13]3[C:14]([C:18]([OH:20])=[O:19])=[CH:15][CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.[OH-].[Mg+2:27].[OH-]>O>[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:23][O:24][CH3:25])[C:8]([NH:10][CH:11]2[C:21](=[O:22])[N:13]3[C:14]([C:18]([O-:20])=[O:19])=[CH:15][CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.[Mg+2:27].[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7](=[N:23][O:24][CH3:25])[C:8]([NH:10][CH:11]2[C:21](=[O:22])[N:13]3[C:14]([C:18]([O-:20])=[O:19])=[CH:15][CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1
Reactant: CON=C(C(=O)NC1C(=O)N2C(C(=O)O)=CCS[C@H]12)c1csc(N)n1
Agent: [Mg+2]
Agent: [OH-]
Solvent: O
Product: CON=C(C(=O)NC1C(=O)N2C(C(=O)[O-])=CCS[C@H]12)c1csc(N)n1
Temperature: 70 °C
Reaction time: 0.5 h

Procedure:
7-[2-(2-Aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid (syn isomer, 1.15 g.) was added to a suspension of magnesium hydroxide (0.088 g.) in water (100 ml.), and the mixture was stirred at 70° C. for 30 minutes to give a solution. After the resultant solution was filtered, the filtrate was lyophilized to give magnesium 7-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylate syn isomer, 1.1 g.).
Reaction SMILES: [OH2:1].[OH-:2].[K+].[C:4]([CH2:6][C:7]1([C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[C:22]([CH3:27])[CH:21]=2)[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1)#N>C(O)C>[C:16]([O:15][C:13]([N:10]1[CH2:11][CH2:12][C:7]([CH2:6][C:4]([OH:2])=[O:1])([C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[C:22]([CH3:27])[CH:21]=2)[CH2:8][CH2:9]1)=[O:14])([CH3:18])([CH3:19])[CH3:17]
Reactant: O
Reactant: Cc1ccc(C2(CC#N)CCN(C(=O)OC(C)(C)C)CC2)cc1C
Reactant: [OH-]
Agent: [K+]
Solvent: CCO
Product: Cc1ccc(C2(CC(=O)O)CCN(C(=O)OC(C)(C)C)CC2)cc1C
Temperature: 90 °C

Procedure:
Water (50 mL) and potassium hydroxide (11.9 g, 213 mmol) were added to a solution of tert-butyl 4-(cyanomethyl)-4-(3,4-dimethylphenyl)piperidine-1-carboxylate 8-4 (14.0 g, 42.6 mmol) in ethanol (200 mL). The reaction was heated at approximately 90° C. until complete conversion of starting material (as monitored by high-pressure liquid chromatography). The reaction mixture was then cooled to ambient temperature, quenched with ice cold 1 N aqueous hydrochloric acid (500 mL) and extracted with ethyl acetate (3×500 mL). The organic phase was washed with brine, dried (magnesium sulfate) and concentrated in vacuo to give a crude residue. Purification of the crude residue by flash chromatography over silica gel (gradient elution; 20%-40% ethyl acetate/hexanes as eluent) afforded compound 8-5 as a white solid.
Reaction SMILES: [CH:1]1([CH2:9][CH2:10][CH2:11][CH2:12][OH:13])[C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[CH2:2]1.[CH3:14][S:15](Cl)(=[O:17])=[O:16].C(N(CC)CC)C>C(Cl)Cl>[S:15]([O:13][CH2:12][CH2:11][CH2:10][CH2:9][CH:1]1[C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[CH2:2]1)(=[O:17])(=[O:16])[CH3:14]
Reactant: CS(=O)(=O)Cl
Reactant: OCCCCC1Cc2ccccc21
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OCCCCC1Cc2ccccc21
Yield: 96 %

Procedure:
4-(benzocyclobutan-1-yl)-butyl mesylate was prepared, in a yield of 96%, by treating 4-(benzocyclobutan-1-yl)butanol (oil) with CH3SO2Cl in the presence of triethylamine in methylene chloride.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH3:22])=[CH:7][N:8]3[C:15](=[O:16])[C:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:13][N:12]=[C:9]32)=[CH:4][CH:3]=1.[S:23](Cl)([CH3:26])(=[O:25])=[O:24]>N1C=CC=CC=1>[S:23]([NH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH3:22])=[CH:7][N:8]3[C:15](=[O:16])[C:14]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:13][N:12]=[C:9]32)=[CH:4][CH:3]=1)([CH3:26])(=[O:25])=[O:24]
Reactant: CS(=O)(=O)Cl
Reactant: CCOC(=O)c1cnc2c3cc(N)ccc3c(C)cn2c1=O
Solvent: c1ccncc1
Product: CCOC(=O)c1cnc2c3cc(NS(C)(=O)=O)ccc3c(C)cn2c1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution oe ethyl 10-amino-7-methyl-4-oxo-4H-pyrimido[2,1-a]isoquinoline-3-carboxylate (800 mg) in pyridine (60 ml) was added mesyl chloride (0.28 ml) at ice bath temperature. The reaction mixture was allowed to stir overnight at room temperature and then concentrated in vacuo. The residue was collected, washed successively with 0.1N hydrochloric acid and water and recrystallized from N,N-dimethylformamide to give ethyl 10-mesylamino-7-methyl-4-oxo-4H-pyrimido[2,1-a]isoquinoline-3-carboxylate (0.76 g).
Reaction SMILES: C=O.[CH3:3][C:4]1([CH3:9])[C:7](=[O:8])[O:6][CH2:5]1.[C:10]([O:15][CH2:16][C:17]([CH3:34])([CH3:33])[C:18]([O:20][C:21](=[O:32])[C:22]([CH3:31])([CH3:30])[CH2:23][O:24][C:25](=O)[CH:26]([CH3:28])[CH3:27])=[O:19])(=O)[CH:11]([CH3:13])[CH3:12]>>[C:18]([O:20][C:21](=[O:32])[CH:22]([CH3:30])[CH3:23])(=[O:19])[CH:17]([CH3:33])[CH3:16].[CH3:3][C:4]1([CH3:9])[C:7](=[O:8])[O:6][CH2:5]1.[CH2:10]([O:15][CH2:16][C:17]([CH3:34])([CH3:33])[C:18]([O:20][C:21](=[O:32])[C:22]([CH3:30])([CH3:31])[CH2:23][O:24][CH2:25][CH:26]([CH3:27])[CH3:28])=[O:19])[CH:11]([CH3:12])[CH3:13]
Reactant: CC(C)C(=O)OCC(C)(C)C(=O)OC(=O)C(C)(C)COC(=O)C(C)C
Agent: C=O
Agent: CC1(C)COC1=O
Product: CC(C)C(=O)OC(=O)C(C)C
Product: CC(C)COCC(C)(C)C(=O)OC(=O)C(C)(C)COCC(C)C
Reaction time: 48 h

Procedure:
This example shows the lower yields and conversions obtained by the usually prepared tantalum oxide on silica gel catalyst. The catalyst is prepared by the same procedure described in Example 1 except that after treatment in air at 550° C. for 1.5 hours the reactor is cooled and put into service. This material is not steam treated at high temperatures. The catalyst is tested as described in Example 2 in continuous operation for two days. For this period formaldehyde conversion to pivalolactone averages 28 percent with 26 percent going to isobutyroxypivalic anhydride. Isobutyric anhydride yield for the same two days averages 30 percent to pivalolactone and 41 percent to isobutyoxypivalic anhydride.
Reaction SMILES: [CH2:1]([O:17][C:18]1[CH:36]=[CH:35][C:21]([O:22][CH2:23][C:24]([NH:26][CH2:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=2)=[O:25])=[CH:20][CH:19]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[CH2:37]([I:39])[CH3:38]>>[I-:39].[CH2:37]([N+:30]1[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=1[CH2:28][CH2:27][NH:26][C:24](=[O:25])[CH2:23][O:22][C:21]1[CH:20]=[CH:19][C:18]([O:17][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])=[CH:36][CH:35]=1)[CH3:38]
Reactant: CCI
Reactant: CCCCCCCCCCCCCCCCOc1ccc(OCC(=O)NCCc2ccccn2)cc1
Product: CCCCCCCCCCCCCCCCOc1ccc(OCC(=O)NCCc2cccc[n+]2CC)cc1
Product: [I-]
Yield: 81.4 %

Procedure:
The title compound is prepared by the procedure of Example 8, using 0.50 g of product from Example 92, 7.85 g of ethyl iodide and heating the mixture at 110°-120° C. for 26 hours. The residue is recrystallized from methyl alcohol to give 0.535 g of the desired product.
Reaction SMILES: C([CH2:3][C:4]([NH:6][C@H:7]1[CH2:12][CH2:11][C@H:10]([O:13][N+:14]([O-:16])=[O:15])[CH2:9][CH2:8]1)=[O:5])#N.C(CC(N[C@H]1CC[C@H](O)CC1)=O)#N>>[C:4]([NH:6][C@H:7]1[CH2:8][CH2:9][C@H:10]([O:13][N+:14]([O-:16])=[O:15])[CH2:11][CH2:12]1)(=[O:5])[CH3:3]
Reactant: N#CCC(=O)N[C@H]1CC[C@H](O[N+](=O)[O-])CC1
Agent: N#CCC(=O)N[C@H]1CC[C@H](O)CC1
Product: CC(=O)N[C@H]1CC[C@H](O[N+](=O)[O-])CC1

Procedure:
2-cyano-N-(trans-4-nitroxycyclohexyl)-acetic acid amide from 2-cyano-N-(trans-4-hydroxycyclohexyl)-acetic acid amide melting point: 149°-150° C. (ether), yield: 53% of theory.
Reaction SMILES: Cl[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH2:11][CH2:12][OH:13].[NH2:14][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][CH:20]([NH:23][C:24]2[N:28]([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=3)[C:27]3[CH:37]=[CH:38][CH:39]=[CH:40][C:26]=3[N:25]=2)[CH2:19][CH2:18]1.C(=O)([O-])[O-].[Na+].[Na+]>O>[F:36][C:33]1[CH:34]=[CH:35][C:30]([CH2:29][N:28]2[C:27]3[CH:37]=[CH:38][CH:39]=[CH:40][C:26]=3[N:25]=[C:24]2[NH:23][CH:20]2[CH2:21][CH2:22][N:17]([CH2:16][CH2:15][NH:14][C:2]3[N:10]=[CH:9][N:8]=[C:7]4[C:3]=3[N:4]=[CH:5][N:6]4[CH2:11][CH2:12][OH:13])[CH2:18][CH2:19]2)=[CH:31][CH:32]=1
Reactant: OCCn1cnc2c(Cl)ncnc21
Reactant: NCCN1CCC(Nc2nc3ccccc3n2Cc2ccc(F)cc2)CC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: OCCn1cnc2c(NCCN3CCC(Nc4nc5ccccc5n4Cc4ccc(F)cc4)CC3)ncnc21
Temperature: 130 °C
Yield: 53 %

Procedure:
A mixture of 2 parts of 6-chloro-9H-purine-9-ethanol, 3.7 parts of N-[1-(2-aminoethyl)-4-piperidinyl]-1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-amine, 1.06 parts of sodium carbonate and 45 parts of N;N-dimethylacetamide was stirred and heated for 3 hours at 130° C. The reaction mixture was poured into water and the product was extracted with 4-methyl-2-pentanone. The extract was dried, filtered and evaporated. The residue was crystallized from acetonitrile. The product was filtered off and dried, yielding 2.8 parts (53%) of 6-[[2-[4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]amino]-1-piperidinyl]ethyl]amino]-9H-purine-9-ethanol; mp. 168.7° C. (compound 93).
Reaction SMILES: ClC1C=C(C=CC=1F)[C:5]1[C:10]([C:11]2[CH:20]=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([C:21]4[N:25]([CH:26]5[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]5)[C:24]5[CH:32]=[CH:33][C:34]([C:36]([OH:38])=[O:37])=[CH:35][C:23]=5[N:22]=4)[CH:17]=3)[N:12]=2)=[CH:9][C:8]([O:39][CH3:40])=[CH:7][CH:6]=1.COC(C1C=CC2N(C3CCCCC3)C(C3C=C4C(=CC=3)N=C(C3C=C(OC)C=CC=3Br)C=C4)=NC=2C=1)=O.[F:83][C:84]1[CH:89]=[CH:88][CH:87]=[CH:86][C:85]=1B(O)O>>[CH:26]1([N:25]2[C:24]3[CH:32]=[CH:33][C:34]([C:36]([OH:38])=[O:37])=[CH:35][C:23]=3[N:22]=[C:21]2[C:16]2[CH:17]=[C:18]3[C:13](=[CH:14][CH:15]=2)[N:12]=[C:11]([C:10]2[C:5]([C:85]4[CH:86]=[CH:87][CH:88]=[CH:89][C:84]=4[F:83])=[CH:6][CH:7]=[C:8]([O:39][CH3:40])[CH:9]=2)[CH:20]=[CH:19]3)[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]1
Reactant: OB(O)c1ccccc1F
Reactant: COc1ccc(-c2ccc(F)c(Cl)c2)c(-c2ccc3cc(-c4nc5cc(C(=O)O)ccc5n4C4CCCCC4)ccc3n2)c1
Agent: COC(=O)c1ccc2c(c1)nc(-c1ccc3nc(-c4cc(OC)ccc4Br)ccc3c1)n2C1CCCCC1
Product: COc1ccc(-c2ccccc2F)c(-c2ccc3cc(-c4nc5cc(C(=O)O)ccc5n4C4CCCCC4)ccc3n2)c1
Yield: 25 %

Procedure:
Following the full procedure and workup for Compound 366, Compound 365b (100 mg, 0.175 mmol) was reacted with 2-fluorophenylboronic acid (37 mg, 0.2625 mmol) to produce the title compound (9 mg, 25% yield).
Reaction SMILES: [OH:1]N1C(=O)CCC1=O.[CH:9]1([C:15]2C=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.[C:21](=[O:23])=[O:22].O=O>C(O)(=O)C.O.O.O.O.C([O-])(=O)C.[Co+2].C([O-])(=O)C>[C:15]([CH2:16][CH2:17][CH2:18][CH2:19][C:21]([OH:23])=[O:22])(=[O:1])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: O=C=O
Reactant: c1ccc(C2CCCCC2)cc1
Reactant: O=C1CCC(=O)N1O
Agent: [Co+2]
Agent: CC(=O)[O-]
Agent: O=O
Solvent: O
Solvent: CC(=O)O
Product: O=C(O)CCCCC(=O)c1ccccc1
Temperature: 100 °C
Reaction time: 6 h
Yield: 70 %

Procedure:
In this example, a solution of 0.1191 g (1.03 mmol) of N-hydroxysuccinimide, 1.1730 g (7.31 mmol) of cyclohexylbenzene and 0.1330 g (0.53 mmol) of cobalt acetate tetrahydrate in 40 ml of acetic acid was heated to 100° C. in a Parr Hastelloy reactor with temperature and pressure transducer. After the temperature reached 100° C., 745 psi of CO2 was introduced into the reactor, then 120 psi of O2 was added slowly to the reactor. The mixture was stirred under pressure for six hours at 100° C., then the pressure was released, and the mixture was cooled to room temperature. The mixture solution was extracted with ethyl acetate then washed with a saturated NaCl solution in water and, dried over Na2SO4 to yield pure white solid 5-benzoylvaleric acid (about 70% yield) after extraction by ethyl acetate with analyses by GC-MS and NMR.
Reaction SMILES: [C:1]12(O)[CH2:10][CH:6]([CH2:7][CH2:8][CH2:9]1)[CH:5]1[CH2:11][CH:2]2[CH2:3][CH2:4]1.S(=O)(=O)(O)[OH:14].[C:18](#[N:20])[CH3:19]>>[C:18]([NH:20][C:1]12[CH2:10][CH:6]([CH2:7][CH2:8][CH2:9]1)[CH:5]1[CH2:11][CH:2]2[CH2:3][CH2:4]1)(=[O:14])[CH3:19]
Reactant: CC#N
Reactant: O=S(=O)(O)O
Reactant: OC12CCCC(C1)C1CCC2C1
Product: CC(=O)NC12CCCC(C1)C1CCC2C1
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 98 %

Procedure:
10.0 Grams (60 millimoles) of tricyclo [4.3.1.12,5 ] undecane-1-ol (X=OH in formula (II)) are dissolved in 120 ml of acetonitrile. The solution is cooled and kept at 0° C, and then 25 ml of concentrated sulfuric acid are added dropwise under stirring over 45 minutes. The stirring is continued further at room temperature for 5 hours. The reaction mixture is placed onto 200 g of ice and extracted twice, each time with 100 ml of diethyl ether. The combined extracts are washed with saturated aqueous solution hydrogencarbonate solution and then with water and dried with anhydrous sodium sulfate. The solvent is distilled out and the residue is recrystallized from acetone-n-hexane to obtain 12.2 g (yield 98%) of 1-acetylaminotricyclo [4.3.1.12,5 ] undecane (I) as white crystals (m.p. 138°-139° C).
Reaction SMILES: [CH3:1][C:2]([O:5][C:6]([NH:8][CH:9]1[CH2:13][NH:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])[CH3:3].C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:21]1[CH:22]=[C:23]([Cl:27])[CH:24]=[CH:25][CH:26]=1.C1(P(C2C=CC=CC=2)C2(P(C3C=CC=CC=3)C3C=CC=CC=3)CC=C3C(C=CC=C3)=C2C2C3C(=CC=CC=3)C=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1>[Cl:27][C:23]1[CH:22]=[C:21]([N:12]2[CH2:11][CH2:10][CH:9]([NH:8][C:6](=[O:7])[O:5][C:2]([CH3:1])([CH3:3])[CH3:4])[CH2:13]2)[CH:26]=[CH:25][CH:24]=1
Reactant: Clc1cccc(Br)c1
Reactant: CC(C)(C)OC(=O)NC1CCNC1
Agent: C1=c2ccccc2=C(c2cccc3ccccc23)C(P(c2ccccc2)c2ccccc2)(P(c2ccccc2)c2ccccc2)C1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)NC1CCN(c2cccc(Cl)c2)C1
Temperature: 110 °C
Reaction time: 15 h
Yield: 62.7 %

Procedure:
3-N-Boc-amino pyrrolidine (120 mg, 0.644 mmol), cesium carbonate (252 mg, 0.773 mmol), and 3-bromochlorobenzene (75.7 μl, 0.644 mmol) were suspended in dry toluene. Argon was bubbled through the suspension for 2 minutes and then tris(dibenyzlideneacetone)dipalladium (35.4 mg, 0.0387 mmol) and rac-2,2-bis(diphenylphosphino)-1,1′-binaphthyl (60.4 mg, 0.0966 mmol) were added. The reaction vial was capped and heated to 110° C. with rapid stirring. After 15 hours, reaction was cooled to ambient temperature and applied directly to a silica gel column. Elution was a gradient of 5-70% ethyl acetate-hexanes provided the title compound (120 mg, 0.404 mmol, 62.8% yield) as an oil.
Reaction SMILES: FC(F)(F)C(O)=O.FC(F)(F)C(O)=O.[NH2:15][CH2:16][C@H:17]1[CH2:22][CH2:21][C@H:20]([N:23]2[C:27]3=[C:28]4[S:34][CH:33]=[CH:32][C:29]4=[N:30][CH:31]=[C:26]3[N:25]=[C:24]2[C@H:35]([OH:37])[CH3:36])[CH2:19][CH2:18]1.C(N(CC)CC)C.Cl[C:46]([O:48][CH3:49])=[O:47]>C(Cl)Cl>[OH:37][C@@H:35]([C:24]1[N:23]([C@H:20]2[CH2:21][CH2:22][C@H:17]([CH2:16][NH:15][C:46](=[O:47])[O:48][CH3:49])[CH2:18][CH2:19]2)[C:27]2=[C:28]3[S:34][CH:33]=[CH:32][C:29]3=[N:30][CH:31]=[C:26]2[N:25]=1)[CH3:36]
Reactant: COC(=O)Cl
Reactant: C[C@@H](O)c1nc2cnc3ccsc3c2n1[C@H]1CC[C@H](CN)CC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)NC[C@H]1CC[C@H](n2c([C@@H](C)O)nc3cnc4ccsc4c32)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of (1R)-1-{1-[trans-4-(aminomethyl)cyclohexyl]-1H-imidazo[4,5-d]thieno[3,2-b]pyridin-2-yl}ethanol bis(trifluoroacetate) (16 mg, 0.029 mmol) and triethylamine (20 μL, 0.14 mmol) in methylene chloride (1 mL) was added methyl chloroformate (2.6 μL, 0.034 mmol). The mixture was stirred at room temperature for 1 h, then stripped to dryness and purified on prep-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (1.4 mg, 13%). LCMS calculated for C19H25N4O3S (M+H)+: m/z=389.2. Found: 389.0. 1H NMR (DMSO-d6, 500 MHz): δ 8.98 (1H, s), 8.02 (1H, d, J=5.5 Hz), 7.66 (1H, d, J=5.5 Hz), 7.24 (1H, m), 5.80 (1H, br s), 5.18 (1H, m), 4.90 (1H, br s), 3.54 (3H, s), 2.96 (2H, m), 2.38 (2H, m), 2.00-1.93 (4H, m), 1.76 (1H, m), 1.65 (3H, d, J=6.5 Hz), 1.21 (2H, m) ppm.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:21])[CH2:16][CH2:17][C:18]([OH:20])=[O:19])=[CH:11][CH:10]=1.C1(N)CCCCC1>C(OCC)(=O)C.CO>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([CH:15]([OH:21])[CH2:16][CH2:17][C:18]([OH:20])=[O:19])=[CH:11][CH:10]=1
Reactant: O=C(O)CCC(=O)c1ccc(-c2ccc(F)cc2Cl)cc1
Solvent: CO
Solvent: NC1CCCCC1
Solvent: CCOC(C)=O
Product: O=C(O)CCC(O)c1ccc(-c2ccc(F)cc2Cl)cc1

Procedure:
Prepared analogous to Example 25 from 4-(2'-chloro4'-fluoro-4-biphenylyl)-4-oxo-butyric acid. Melting point 78°-79° C. (from benzene/petroleum ether 3:2); melting point of the cyclohexylamine salt: 161°-162° C. (from ethyl acetate/methanol 1:1).
Reaction SMILES: Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[CH:10]([Mg]Cl)([CH3:12])[CH3:11].[Li+].[Cl-].C(=O)C1C=CC=CC=1>C1COCC1>[CH2:12]([C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1)[CH:10]=[CH2:11]
Reactant: N#Cc1ccc(Br)cc1
Reactant: CC(C)[Mg]Cl
Agent: [Cl-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O=Cc1ccccc1
Product: C=CCc1ccc(C#N)cc1
Yield: 81 %

Procedure:
Highly substituted chloro and methoxy aryl bromides can readily be converted into the desired Grignard reagents 3i, j. After the reaction with ClPPh2 and oxidative work-up, the phosphine oxides 2ia, ja are obtained in good yields (entry 15, 16). This type of compound is of interest in relation with P-ligands for asymmetric catalysis.[5] Also functions like a cyano group are tolerated. Thus, the reaction of 4-bromobenzonitrile in THF at −7° C. leads to the desired arylmagnesium reagent (3d) in only 50% conversion using i-PrMgCl whereas over 90% is observed with i-PrMgCl.LiCl (Scheme 3). The addition of benzaldehyde provides the alcohol 2da in 81% yield whereas allylation of arylmagnesium reagent (3d) with allyl bromide leads to the corresponding 4-allylbenzonitrile in 92% yield (entry 5,6 of Table 1). See FIG. 3 for additional information.
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[Cl:12][C:13]1[C:18]2[O:19][C@@H:20]([CH2:23][OH:24])[CH2:21][O:22][C:17]=2[CH:16]=[CH:15][CH:14]=1.Cl>N1C=CC=CC=1>[C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7]([O:24][CH2:23][C@@H:20]2[O:19][C:18]3[C:13]([Cl:12])=[CH:14][CH:15]=[CH:16][C:17]=3[O:22][CH2:21]2)(=[O:9])=[O:8])=[CH:3][CH:2]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: OC[C@H]1COc2cccc(Cl)c2O1
Agent: Cl
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OC[C@H]2COc3cccc(Cl)c3O2)cc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A solution of 4-toluenesulphonyl chloride (3.15 g) in dry pyridine (15 ml) was added to a solution of (S)-8-chloro-1,4-benzodioxan-2-ylmethanol (3.32 g; prepared in a similar manner to that described above) in dry pyridine (40 ml) and the mixture stirred at ambient temperature for 18 hours, then poured onto ice and dilute hydrochloric acid added to give pH4. The mixture was extracted with dichloromethane (2×200 ml) and the combined extracts washed with brine and dried over magnesium sulphate. The solvent was evaporated to give (R)-8-chloro-1,4-benzodioxan-2-ylmethyl 4-toluenesulphonate (5.21 g) as a pale yellow solid.