Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:17])[CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([F:15])[CH:13]=2)[NH:8][C:7]=1[CH3:16])[CH3:2].[H-].[Na+].Br[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][C:23]=1[C:32]([F:35])([F:34])[F:33].[I-].[Na+]>CS(C)=O.O>[CH2:1]([O:3][C:4](=[O:17])[CH2:5][C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([F:15])[CH:13]=2)[N:8]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][C:23]=2[C:32]([F:34])([F:33])[F:35])[C:7]=1[CH3:16])[CH3:2]
Reactant: CS(=O)(=O)c1ccc(CBr)c(C(F)(F)F)c1
Reactant: CCOC(=O)Cc1c(C)[nH]c2ccc(F)cc12
Agent: [H-]
Agent: [I-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CCOC(=O)Cc1c(C)n(Cc2ccc(S(C)(=O)=O)cc2C(F)(F)F)c2ccc(F)cc12
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a stirring solution of (5-fluoro-2-methyl-1H-indol-3-yl)-acetic acid ethyl ester (100 mg, 0.43 mmol) in dry DMSO (2 ml) at room temperature, is added sodium hydride (26 mg, 0.65 mmol) as a 60% dispersion in mineral oil. After stirring at room temperature for 30 mins, 1-bromomethyl-4-methanesulfonyl-2-trifluoromethyl-benzene (216 mg, 0.68 mmol) (intermediate 1c) and sodium iodide (102 mg, 0.68 mmol) are added. The reaction mixture is stirred at room temperature for 60 h. The reaction mixture is poured into water (20 ml) and extracted with EtOAc (20 ml). The organic phase is dried (MgSO4) and evaporated to dryness in vacuo. The crude product is purified by reverse phase chromatography on a C18 Isolute™ cartridge, eluting in 0-100% MeCN in water, using a FlashMaster Personal™ and GradMaster™; [M+H]+ 472.
Reaction SMILES: C(OC([N:8]1[CH:13]2[CH2:14][CH2:15][CH:9]1[CH2:10][CH:11]([C:16]1[CH:21]=[CH:20][C:19]([N:22]3[CH2:27][CH2:26][N:25]([S:28]([CH3:31])(=[O:30])=[O:29])[CH2:24][CH2:23]3)=[CH:18][CH:17]=1)[CH2:12]2)=O)(C)(C)C.Cl.O1CCOCC1>ClCCl>[CH3:31][S:28]([N:25]1[CH2:24][CH2:23][N:22]([C:19]2[CH:18]=[CH:17][C:16]([CH:11]3[CH2:10][CH:9]4[NH:8][CH:13]([CH2:14][CH2:15]4)[CH2:12]3)=[CH:21][CH:20]=2)[CH2:27][CH2:26]1)(=[O:29])=[O:30]
Reactant: CC(C)(C)OC(=O)N1C2CCC1CC(c1ccc(N3CCN(S(C)(=O)=O)CC3)cc1)C2
Agent: Cl
Solvent: ClCCl
Solvent: C1COCCO1
Product: CS(=O)(=O)N1CCN(c2ccc(C3CC4CCC(C3)N4)cc2)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 86.3 %

Procedure:
3-[4-(4-Methanesulfonylpiperazin-1-yl)phenyl]-8-azabicyclo[3.2.1]octane-8-carboxylic acid tert-butyl ester (0.758 g, 1.69 mmol) is solubilized in 158 ml of dichloromethane. 4N HCl in dioxane (4.2 ml, 16.8 mmol) is then added. After stirring for 16 h at ambient temperature, the reaction medium is concentrated, taken up with water, and washed with ethyl acetate. The pH of the aqueous phase is then adjusted to 10 with a 5N aqueous solution of sodium hydroxide. After extraction with dichloromethane, and washing with water and then with a saturated aqueous sodium chloride solution, the organic phase is dried over MgSO4 and then concentrated to dryness. 0.51 g of expected 3-[4-(4-methanesulfonylpiperazin-1-yl)phenyl]-8-aza-bicyclo[3.2.1]octane is obtained, which is subsequently used as it is.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH:10]=O)=[CH:6][CH:5]=1.[NH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>O.ClCCCl>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:6][CH:5]=1
Reactant: COC(=O)c1ccc(C=O)cc1
Reactant: C1COCCN1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCCl
Product: COC(=O)c1ccc(CN2CCOCC2)cc1
Temperature: 10 °C
Reaction time: 0.08 h

Procedure:
A 2 L, three-neck flask fitted with a mechanical stirrer, addition funnel, and thermocouple probe was charged with 4-formyl-benzoic acid methyl ester (50.0 g, 0.31 mol, 1.0 eq) and 1,2-dichloroethane (700 mL). The resulting mixture was cooled to 10° C. Morpholine (53 mL, 0.61 mol, 2.0 eq) was then added dropwise over 10 min. After 5 min, sodium triacetoxyborohydride (90 g, 0.43 mol, 1.4 eq) was added in portions over 5 min. After stirring 30 min, the reaction mixture was warmed to room temperature. At this point, a slow and steady temperature increase was observed, and a water bath was used to keep the temperature of the reaction mixture below 25° C. The reaction mixture was stirred for 22 hrs at room temperature. Water/ice (100 mL) was added to the reaction and the reaction mixture was stirred for 15 min. NaOH solution (1.0 M in water, 400 mL) was added in several portions, followed by the addition of water (250 mL). The resulting mixture was stirred for 45 min. The layers were separated, and the aqueous layer was extracted with dichloromethane (150 mL). The combined organic layer was washed with brine (150 mL) and then dried over Na2SO4. The solvent was removed in vacuo to yield the title compound as a pale yellow, viscous oil.
Reaction SMILES: C(=O)(OC(C)(C)C)N.[CH3:9][O:10][C:11]([C:13]1[CH:18]=[CH:17][C:16]([C@@H:19]([NH:21][C:22]([C@H:24]2[CH2:29][CH:28]3[CH:26]([CH2:27]3)[N:25]2C(OC(C)(C)C)=O)=[O:23])[CH3:20])=[CH:15][CH:14]=1)=[O:12]>>[CH:26]12[CH2:27][CH:28]1[CH2:29][C@H:24]([C:22]([NH:21][C@H:19]([C:16]1[CH:15]=[CH:14][C:13]([C:11]([O:10][CH3:9])=[O:12])=[CH:18][CH:17]=1)[CH3:20])=[O:23])[NH:25]2
Reactant: COC(=O)c1ccc([C@H](C)NC(=O)[C@H]2CC3CC3N2C(=O)OC(C)(C)C)cc1
Agent: CC(C)(C)OC(N)=O
Product: COC(=O)c1ccc([C@H](C)NC(=O)[C@H]2CC3CC3N2)cc1
Yield: 99.5 %

Procedure:
The title compounds (D107) (48 mg) was prepared according to the general procedure for t-Butyl carbamate (Boc) cleavage starting from (3R)-tert-butyl 3-(((S)-1-(4-(methoxycarbonyl)phenyl)ethyl)carbamoyl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (single diastereoisomer) (D74b) (65 mg)
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:19])([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=1.Cl[CH2:21][CH2:22][NH:23][CH2:24][CH2:25]Cl.Cl>C1(C)C(C)=CC=CC=1>[CH3:19][C:8]([C:5]1[CH:6]=[CH:7][C:2]([N:1]2[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]2)=[CH:3][CH:4]=1)([C:9]([O:11][CH2:12][CH3:13])=[O:10])[C:14]([O:16][CH2:17][CH3:18])=[O:15]
Reactant: ClCCNCCCl
Reactant: CCOC(=O)C(C)(C(=O)OCC)c1ccc(N)cc1
Agent: Cl
Solvent: Cc1ccccc1C
Product: CCOC(=O)C(C)(C(=O)OCC)c1ccc(N2CCNCC2)cc1
Yield: 63.5 %

Procedure:
A suspension of diethyl 2-(4-aminophenyl)-2-methylmalonate (6.00 g, 22.6 mmol), Bis-(2-chloroethyl) amine.HCl (4.82 g, 27.2 mmol) in xylene (20 ml) was refluxed for 48 h. The reaction mixture was concentrated in vacuo and the residue was partitioned between saturated sodium bicarbonate solution and ethyl acetate. The separated organic layer was washed with water, brine solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford crude product. Purification by column chromatography over neutral alumina using 5% MeOH in CHCl3 as eluent afford 4.80 g (63.5%) of diethyl 2-methyl-2-(4-(piperazin-1-yl)phenyl)malonate as brown oil.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[CH3:11][N:12]1[CH2:17][CH2:16][CH:15]([CH2:18][OH:19])[CH2:14][CH2:13]1.[H-].[Na+]>CS(C)=O>[CH3:11][N:12]1[CH2:17][CH2:16][CH:15]([CH2:18][O:19][C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[CH2:14][CH2:13]1
Reactant: CN1CCC(CO)CC1
Reactant: O=[N+]([O-])c1ccc(Cl)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CN1CCC(COc2ccc([N+](=O)[O-])cc2)CC1
Temperature: 40 °C
Reaction time: 2 h
Yield: 69.4 %

Procedure:
To a mixture of p-chloro nitrobenzene (6.0 g, 38 mmol) and 1-methyl-4-piperidinemethanol (4.91 g, 38 mmol) in anhydrous DMSO (60 mL) was added NaH (1.82 g, 45.6 mmol) in small portions at room temperature under N2-atmosphere. After the addition was complete the reaction mixture was warmed at 40° C. and stirred for another 2 h. The reaction was quenched with water, and the product was extracted with EtOAc. The organic layer was washed with brine and dried over Na2SO4. The crude product was recrystallized from ether to yield 6.6 g (69%) of the title compound as an orange solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.59-1.72 (m, 2H) 1.92 (d, J=11.37 Hz, 3 H) 2.19 (t, J=11.49 Hz, 2H) 2.44 (s, 3H) 3.09 (d, J=11.12 Hz, 2H) 3.93 (d, J=5.31 Hz, 2 H) 6.93 (d, J=9.2 Hz, 2H) 8.20 (d, J=9.6 Hz, 2H); [M+H] calc'd for C13H19N2O3, 251.2; found, 251.4.
Reaction SMILES: [Cl-].[Cl:2][C:3]1[C:12]2[C:7](=[CH:8][C:9]([C:13]#[N:14])=[CH:10][CH:11]=2)[CH:6]=[CH:5][C:4]=1[O:15][CH2:16][CH2:17][NH3+:18].[Cl:19][C:20]1[O:24][C:23]([CH:25]=O)=[CH:22][CH:21]=1>>[Cl:2][C:3]1[C:4]([O:15][CH2:16][CH2:17][NH:18][CH2:25][C:23]2[O:24][C:20]([Cl:19])=[CH:21][CH:22]=2)=[CH:5][CH:6]=[C:7]2[C:12]=1[CH:11]=[CH:10][C:9]([C:13]#[N:14])=[CH:8]2
Reactant: N#Cc1ccc2c(Cl)c(OCC[NH3+])ccc2c1
Reactant: O=Cc1ccc(Cl)o1
Agent: [Cl-]
Product: N#Cc1ccc2c(Cl)c(OCCNCc3ccc(Cl)o3)ccc2c1
Yield: 60 %

Procedure:
Prepared from 2-[(1-chloro-6-cyanonaphthalen-2-yl)oxy]ethanaminium chloride and 5-chlorofuran-2-carbaldehyde in 60% yield as a yellow oil.
Reaction SMILES: Cl[C:2]1[CH:13]=[C:6]2[C:7](OC(=O)[NH:11][C:5]2=[CH:4][CH:3]=1)=[O:8].[Cl:14][C:15]1[CH:23]=[C:22]2[C:18]([C:19](=[O:25])[C:20](=O)[NH:21]2)=[CH:17][CH:16]=1.FC1C=C2C(=CC=1)NC(=O)C2=O>>[Cl:14][C:15]1[CH:23]=[C:22]2[C:18]([C:19](=[O:25])[C:20]3[N:21]2[C:7](=[O:8])[C:6]2[C:5](=[CH:4][CH:3]=[CH:2][CH:13]=2)[N:11]=3)=[CH:17][CH:16]=1
Reactant: O=C1Nc2cc(Cl)ccc2C1=O
Reactant: O=c1[nH]c2ccc(Cl)cc2c(=O)o1
Agent: O=C1Nc2ccc(F)cc2C1=O
Product: O=C1c2ccc(Cl)cc2-n2c1nc1ccccc1c2=O
Yield: 14 %

Procedure:
Using the procedure in Example 12 and substituting isatoic anhydride for 5-chloroisatoic anhydride and 6-chloroisatin for 5-fluoroisatin gave the title compound in 14% yield: mp 300.6°-303.1° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.49 (d, 1H) 8.35 (d, 1H) 7.89 (d, 2H) 7.94 (d, 1H) 7.72-7.82 (m, 1H) 7.55-7.62 (m, 1H); MS (M+CH4CN)+ 324.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:3]=1[CH:4]=O.[NH:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1.[BH4-].[Na+]>C(Cl)Cl>[Br:1][C:2]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:3]=1[CH2:4][N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1
Reactant: C1COCCN1
Reactant: O=Cc1cc(C(F)(F)F)ccc1Br
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Product: FC(F)(F)c1ccc(Br)c(CN2CCOCC2)c1
Reaction time: 0.33 h

Procedure:
2-Bromo-5-(trifluoromethyl)benzaldehyde (266 mg, 1.05 mmol) and morpholine (0.10 mL, 1.2 mmol) were dissolved in DCM (2 mL), stirred for 20 minutes, and then treated with NaBH4 (79 mg, 2.1 mmol). The reaction was stirred overnight at rt, after which time, the reaction was quenched by the slow addition of water (10 mL). The aqueous layer was further extracted with DCM (3×10 mL), dried over sodium sulfate, filtered, and concentrated to dryness. The crude product was purified by FCC to provide the title compound. 1H NMR (500 MHz, CDCl3) δ 7.77 (s, 1H), 7.67 (d, J=8.3, 1H), 7.37 (d, J=8.3, 1H), 3.80-3.69 (m, 4H), 3.63 (d, J=1.7, 2H), 2.59-2.49 (m, 4H).
Reaction SMILES: C1(O[C:8](=[O:26])[NH:9][CH2:10][CH:11]2[CH2:16][CH2:15][C:14]([N:23]([CH3:25])[CH3:24])([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)C=CC=CC=1.[NH:27]1[CH2:31][CH2:30][CH:29]([C:32]2[C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[NH:34][CH:33]=2)[CH2:28]1>O1CCOCC1>[CH3:25][N:23]([CH3:24])[C:14]1([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:13][CH2:12][CH:11]([CH2:10][NH:9][C:8]([N:27]2[CH2:31][CH2:30][CH:29]([C:32]3[C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[NH:34][CH:33]=3)[CH2:28]2)=[O:26])[CH2:16][CH2:15]1
Reactant: c1ccc2c(C3CCNC3)c[nH]c2c1
Reactant: CN(C)C1(c2ccccc2)CCC(CNC(=O)Oc2ccccc2)CC1
Solvent: C1COCCO1
Product: CN(C)C1(c2ccccc2)CCC(CNC(=O)N2CCC(c3c[nH]c4ccccc34)C2)CC1
Yield: 37.3 %

Procedure:
The diastereoisomer mixture of (4-dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid phenyl ester (519 mg, 1.47 mmole) was added to a solution of 3-pyrrolidine-3-yl-1H-indole (274 mg, 1.47 mmole) in dioxane (12 ml). The reaction mixture was then boiled under reflux for 12 hours. The reaction mixture was worked up by distilling off the solvent. The residue contained, apart from phenol, also the two diastereoisomers of 3-(1H-indol-3-yl)pyrrolidine-1-carboxylic acid-(4-dimethyl amino-4-phenylcyclohexylmethyl)-amide. The diastereoisomers were separated and purified by flash chromatography on silica gel (50 g). Methanol/EE (1:1; 1000 ml) was used as eluent. The non-polar diastereoisomer of 3-(1H-indol-3-yl)pyrrolidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide (234 mg, m.p. 101°-103° C., 36%) and the polar diastereoisomer of 3-(1H-indol-3-yl)pyrrolidine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide (244 mg, m.p. 103°-106° C., 37%) were thereby obtained in pure form.
Reaction SMILES: [CH3:1][C:2]1[C:3]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[N:4][C:5]([CH3:9])=[C:6]([CH3:8])[CH:7]=1.[I:16][C:17]1[CH:25]=[CH:24][C:20]([C:21](Cl)=[O:22])=[CH:19][CH:18]=1>>[I:16][C:17]1[CH:25]=[CH:24][C:20]([C:21]([N:13]2[CH2:12][CH2:11][N:10]([C:3]3[C:2]([CH3:1])=[CH:7][C:6]([CH3:8])=[C:5]([CH3:9])[N:4]=3)[CH2:15][CH2:14]2)=[O:22])=[CH:19][CH:18]=1
Reactant: Cc1cc(C)c(N2CCNCC2)nc1C
Reactant: O=C(Cl)c1ccc(I)cc1
Product: Cc1cc(C)c(N2CCN(C(=O)c3ccc(I)cc3)CC2)nc1C
Yield: 94.8 %

Procedure:
By reaction and treatment in the same manner as in Preparation Example 161 and using 1-(3,5,6-trimethylpyridin-2-yl)piperazine (4.39 g) described in Preparation Example 175 and 4-iodobenzoyl chloride (5.98 g), the title compound (8.82 g) was obtained.
Reaction SMILES: [CH3:1][C:2]1[C:6]([CH:7]([C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)[CH2:8][C:9]([OH:11])=[O:10])=[C:5]([CH3:19])[O:4][N:3]=1.[CH3:20]S(O)(=O)=O>CO>[CH3:1][C:2]1[C:6]([CH:7]([C:12]2[CH:13]=[CH:14][C:15]([OH:18])=[CH:16][CH:17]=2)[CH2:8][C:9]([O:11][CH3:20])=[O:10])=[C:5]([CH3:19])[O:4][N:3]=1
Reactant: CS(=O)(=O)O
Reactant: Cc1noc(C)c1C(CC(=O)O)c1ccc(O)cc1
Solvent: CO
Product: COC(=O)CC(c1ccc(O)cc1)c1c(C)noc1C
Temperature: 65 °C
Reaction time: 1 h
Yield: 18.72 %

Procedure:
To a 25 mL RB flask fitted with magnetic stirrer was charged 20 mL of methanol. To the stirred solvent was added 3-(3,5-Dimethyl-1,2-oxazol-4-yl)-3-(4-hydroxyphenyl)propanoic acid (1.0 g, 6.1 mmol), followed by methanesulfonic acid (1.16 g, 12.0 mmol). After addition, the RM was refluxed at 65° C. for 1 h. After 1 h, the solvent was evaporated, water (20 mL) was added and the organic layer was extracted with ethyl acetate (15 mL×2). The organic layer was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The product was obtained as brown liquid. (0.2 g, yield: 18.72%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.C([O-])([O-])=O.[Na+].[Na+].I[C:17]1[CH:22]=[CH:21][C:20]([S:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)(=[O:25])=[O:24])=[C:19]([N+:32]([O-:34])=[O:33])[CH:18]=1.O>C(O)C.O>[N+:32]([C:19]1[CH:18]=[C:17]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[CH:22]=[CH:21][C:20]=1[S:23]([C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)(=[O:25])=[O:24])([O-:34])=[O:33]
Reactant: O=[N+]([O-])c1cc(I)ccc1S(=O)(=O)c1ccccc1
Reactant: OB(O)c1cccnc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: O=[N+]([O-])c1cc(-c2cccnc2)ccc1S(=O)(=O)c1ccccc1
Temperature: 90 °C
Reaction time: 0.5 h
Yield: 70.5 %

Procedure:
Argon was passed through a mixture of 3-pyridineboronic acid (187 mg, 1.53 mmol) and Na2CO3 (408 mg, 3.84 mmol) in water ethanol (water 3.74 ml, ethanol 14.96 ml) at stirring at 90° C. for 30 min and cooled to 80° C. 4-Iodo-2-nitro-1-(phenylsulfonyl)-benzene 4(3) (734 mg, 1.9 mmol) was added to the reaction mixture in argon current, inert gas was passed for another 10 min, then bis-triphenylphosphinepalladium dichloride (34 mg) was added and argon was passed for additional 5 min. The reaction mixture was stirred for 2 h at 85° C. in argon atmosphere, then, cooled, water was added, and precipitated solid was filtered off. The reaction product was extracted from mother liquor with CH2Cl2, organic layer was dried over Na2SO4, filtered and evaporated to dryness. The residue was suspended in CH2Cl2, filtered off, mother liquor was evaporated, the residue washed with diethyl ether, it gave 460 mg (70.5%) of 3-(3-nitro-4-(phenylsulfonyl)phenyl)pyridine 5(1).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH3:8])[C:3]=1[CH3:9].[B:10](OC(C)C)([O:15]C(C)C)[O:11]C(C)C.[Li]CCCC>C1COCC1.C1(C)C=CC=CC=1>[CH3:8][C:4]1[C:3]([CH3:9])=[C:2]([B:10]([OH:15])[OH:11])[CH:7]=[CH:6][N:5]=1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Reactant: Cc1nccc(Br)c1C
Agent: [Li]CCCC
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: Cc1nccc(B(O)O)c1C
Temperature: -20 °C
Reaction time: 2 h

Procedure:
A solution of 4-bromo-2,3-dimethyl-pyridine (1.38 g) and triisopropyl borate (2.05 mL) in 4 mL dry THF and 14 mL dry toluene was stirred on a dry ice-acetone bath to an internal temperature of −65° C. and 3.56 mL n-BuLi in hexanes was added dropwise over 0.5 h. Stirring continued at −65° C. for additional 2 h, then the bath was removed the mixture allowed to warm to −20° C. Reaction was quenched by addition of 10 mL 2M HCl, then allowed to warm to rt and diluted with more THF. 5M NaOH was added until the mixture reached pH 7, layers formed and the organic layer was collected. Several more extractions with THF were done and the combined organic extracts were dried with brine and Na2SO4 and concentrated under reduced pressure. The product crystallized and two crops were collected, for a total of 304 mg of 2,3-dimethylpyridine-4-boronic acid. LCMS (m/z) 153.
Reaction SMILES: O[C:2]1[CH:3]=[C:4]([CH:7]=[C:8](O)[CH:9]=1)[CH2:5][OH:6].[C:11]([O-:19])(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[C:5]([O:19][C:11](=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)(=[O:6])[C:4]1[CH:7]=[CH:8][CH:9]=[CH:2][CH:3]=1
Reactant: OCc1cc(O)cc(O)c1
Reactant: O=C([O-])c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: O=C(OC(=O)c1ccccc1)c1ccccc1

Procedure:
The synthesis of organotelluride catalysts based on 3,5-dihydroxybenzyl alcohol (1) is shown in FIG. 11. 3,5-Bis[3-(tert-butyldimethylsilyloxy)propyl-1-oxy]benzyl alcohol (5) (Francavilla et al., J. Am. Chem. Soc., 123:57 et al. (2001), which is hereby incorporated by reference in its entirety) was converted to the corresponding benzoate 6 in 99% isolated yield with benzoic anhydride and pyridine in the presence of catalytic DMAP. The silyl protecting groups were removed with HF-pyridine to give diol 7 in 89% isolated yield. Diol 7 was converted to the corresponding dibromide 8 in two steps (Wendler et al., Tetrahedron, 3:144 et al. (1958), which is hereby incorporated by reference in its entirety). The mesylate was first prepared, but not isolated, and was then treated in situ with lithium bromide to give dibromide 8 in 87% isolated yield. The addition of PhTeNa to 8 gave 9a with two phenyltelluro groups in 65% isolated yield; 4-Me2NC6H4TeNa, 9b with two dimethylaminophenyltelluro groups in 92% isolated yield; and n-C6H13TeNa, 9c with two hexyltelluro groups in 62% isolated yield.
Reaction SMILES: [CH3:1][C:2]([CH3:12])=[CH:3][CH:4]1[CH:6]([C:7]([OH:9])=[O:8])[C:5]1([CH3:11])[CH3:10].[F:13][CH:14](Br)[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:16]=1>>[CH3:1][C:2]([CH3:12])=[CH:3][CH:4]1[CH:6]([C:7]([O:9][CH:14]([F:13])[C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:16]=2)=[O:8])[C:5]1([CH3:11])[CH3:10]
Reactant: CC(C)=CC1C(C(=O)O)C1(C)C
Reactant: FC(Br)c1cccc(Oc2ccccc2)c1
Product: CC(C)=CC1C(C(=O)OC(F)c2cccc(Oc3ccccc3)c2)C1(C)C

Procedure:
This compound was prepared from 3-(2-methylprop-1-enyl)-2,2-dimethylcyclopropanecarboxylic acid and α-fluoro-3-phenoxybenzylbromide following the procedure described in Example 2 Method B. The product, a colourless oil, was characterised by pmr spectroscopy. Chemical shift δppm (solvent CDCl3): 1.24 (6H, m, C(CH3)2); 1.70 (6H, s, (CH3)2C=); about 1.9 (2H, m, cyclopropyl protons); 4.93 and 5.43 (1H, 2xd, J=7 Hz, vinyl proton); 7.13 (1H, d, J=56 Hz, CHF); about 7.1 (9H, m, aromatic protons).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:14])[C:5]1[CH:10]=[C:9]([Cl:11])[C:8](N)=[C:7]([Cl:13])[CH:6]=1)[CH3:2].CS(O)(=O)=O.N(OCCC(C)C)=O.[SH:28][CH2:29][C:30]([OH:32])=[O:31]>C(O)(=O)C.ClCCl>[CH2:1]([O:3][C:4](=[O:14])[C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([S:28][CH2:29][C:30]([OH:32])=[O:31])=[C:7]([Cl:13])[CH:6]=1)[CH3:2]
Reactant: O=C(O)CS
Reactant: CCOC(=O)c1cc(Cl)c(N)c(Cl)c1
Agent: CC(C)CCON=O
Agent: CS(=O)(=O)O
Solvent: ClCCl
Solvent: CC(=O)O
Product: CCOC(=O)c1cc(Cl)c(SCC(=O)O)c(Cl)c1
Reaction time: 0.5 h

Procedure:
4-Amino-3,5-dichlorobenzoic acid ethyl ester (17.7 g) was dissolved in a mixture of acetic acid (75 mL) and dichloromethane (75 mL) and then methanesulfonic acid (22 mL) was added. 3-Methylbutyl nitrite (10 mL) was added to the solution while the temperature was kept at 0-5° C. After 30 min, mercaptoacetic acid (38 mL) was added at 0-5° C. Then a part of the dichloromethane was removed by distillation which was stopped when the internal temperature of the mixture was 80° C. and this temperature was kept for additional 45 min. The mixture was cooled and the rest of the solvents were evaporated under vacuum. Toluene (300 mL), water (200 mL) and hydrochloric acid (6 M, 80 mL) were added. The organic phase was separated and then extracted with potassium bicarbonate solution (1 M, 200 mL) which was acidified with hydrochloric acid (6M, 50 mL). The product was extracted to toluene (100 mL) which was dried (sodium sulphate) and evaporated to dryness (yield 5.1 g). 1H-NMR (400 MHz, DMSO-d6) d=1.33 (t, J=7.0 Hz, 3H), 3.74 (s, 2H), 4.34 (q, J=7.0 Hz, 2H), 7.97 (s, 2H), 12.5 (b, 1H).
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1.S(Cl)([Cl:16])=O>C1C=CC=CC=1>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([Cl:16])=[O:7])=[C:4]([N+:11]([O-:13])=[O:12])[CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1ccc(F)cc1[N+](=O)[O-]
Solvent: c1ccccc1
Product: O=C(Cl)c1ccc(F)cc1[N+](=O)[O-]
Reaction time: 5 h

Procedure:
To a stirred mixture of 76 parts of 4-fluoro-2-nitrobenzoic acid and 225 parts of benzene are added dropwise 71 parts of sulfinyl chloride. Upon completion, stirring is continued first for 5 hours at reflux and further overnight at room temperatue. The reaction mixture is evaporated. The residue is taken up twice in benzene and the latter is evaporated each time, yielding 85 parts of 4-fluoro-2-nitrobenzoyl chloride as a residue.
Reaction SMILES: C(=O)([O-])[O-].[La+3:5].C(=O)([O-])[O-].C(=O)([O-])[O-].[La+3].[F:15][C:16]([F:22])([F:21])[S:17]([OH:20])(=[O:19])=[O:18]>O>[F:15][C:16]([F:22])([F:21])[S:17]([O-:20])(=[O:19])=[O:18].[La+3:5].[F:15][C:16]([F:22])([F:21])[S:17]([O-:20])(=[O:19])=[O:18].[F:15][C:16]([F:22])([F:21])[S:17]([O-:20])(=[O:19])=[O:18]
Reactant: O=S(=O)(O)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [La+3]
Solvent: O
Product: O=S(=O)([O-])C(F)(F)F

Procedure:
Lanthanum carbonate (15 g.) and trifluoromethanesulfonic acid (22.5 g) are combined as described in Example II. The solution is evaporated at reduced pressure and the residue, dried over sulfuric acid in dessicator. The product obtained, 20.4 g., gave the following analysis: % La 22.06; % S 15.88; % H2O 5.61, indicating an Al:S ratio of 1:3.12.