Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([NH:5][S:6]([C:9]1[CH:14]=[C:13]([N+:15]([O-])=O)[CH:12]=[CH:11][C:10]=1[C:18]([O:20][CH3:21])=[O:19])(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>CO>[C:1]([NH:5][S:6]([C:9]1[CH:14]=[C:13]([NH2:15])[CH:12]=[CH:11][C:10]=1[C:18]([O:20][CH3:21])=[O:19])(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COC(=O)c1ccc([N+](=O)[O-])cc1S(=O)(=O)NC(C)(C)C
Reactant: [H][H]
Solvent: CO
Product: COC(=O)c1ccc(N)cc1S(=O)(=O)NC(C)(C)C

Procedure:
25.08 g (0.079 mol) of N-tert-butyl-2-methoxycarbonyl-5-nitrobenzenesulfonamide are dissolved in 1000 ml of MeOH. 0.50 g of Pd--C (10%) is added and the mixture is shaken under a hydrogen atmosphere (1 atm) until the uptake of hydrogen has finished. The catalyst is separated off and the solvent is removed by distillation. The residue is induced to crystallize by stirring with a little ethyl acetate. The resulting N-tert-butyl-5-amino-2-methoxycarbonylbenzenesulfonamide (18.3 g; 80.9% of theory) melts at 193° C.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][N:8]=[C:9]([F:12])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:13]#[N:14].[Cl:15][C:16]1[CH:17]=[C:18]([CH:20]=[CH:21][C:22]=1[F:23])[NH2:19]>COCCOC>[Cl:15][C:16]1[CH:17]=[C:18]([NH:19][C:2]2[C:11]3[C:6](=[CH:7][N:8]=[C:9]([F:12])[CH:10]=3)[N:5]=[CH:4][C:3]=2[C:13]#[N:14])[CH:20]=[CH:21][C:22]=1[F:23]
Reactant: N#Cc1cnc2cnc(F)cc2c1Cl
Reactant: Nc1ccc(F)c(Cl)c1
Solvent: COCCOC
Product: N#Cc1cnc2cnc(F)cc2c1Nc1ccc(F)c(Cl)c1
Temperature: 140 °C
Yield: 75.3 %

Procedure:
In a microwave vial, 4-chloro-6-fluoro-1,7-naphthyridine-3-carbonitrile (1.3 g, 6.3 mmol) and 3-chloro-4-fluoroaniline (1.0 g, 6.9 mmol) were taken up in DME. The vial was crimp-sealed and heated in a microwave reactor at 140° C. for 15 minutes. This was repeated with another two batches of reagents. The contents of the three vials were transferred together to a separatory funnel and partitioned between EtOAc and 10% Na2CO3, and the aqueous layer extracted two additional times with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4, filtered and evaporated to give 4-(3-chloro-4-fluorophenylamino)-6-fluoro-1,7-naphthyridine-3-carbonitrile of sufficient purity to be used directly in the next step (4.6 g, 75.3% yield): 1H NMR (400 MHz, DMSO-D6) δ 7.32-7.49 (m, 1 H) 7.53 (t, J=9.0 Hz, 1 H) 7.72 (dd, J=6.3, 2.3 Hz, 1 H) 8.16 (s, 1 H) 8.69 (s, 1 H) 9.08 (s, 1 H) 10.14 (s, 1 H).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([OH:15])[CH:10]=2)[C:5]([F:16])=[CH:4][N:3]=1.[O:17]1[C:22]2[CH:23]=[CH:24][C:25]([CH2:27][NH2:28])=[CH:26][C:21]=2[O:20][CH2:19][CH2:18]1.N1C=CC(N)=NC=1N>>[O:17]1[C:22]2[CH:23]=[CH:24][C:25]([CH2:27][NH:28][C:2]3[N:7]=[C:6]([NH:8][C:9]4[CH:14]=[CH:13][CH:12]=[C:11]([OH:15])[CH:10]=4)[C:5]([F:16])=[CH:4][N:3]=3)=[CH:26][C:21]=2[O:20][CH2:19][CH2:18]1
Reactant: NCc1ccc2c(c1)OCCO2
Reactant: Oc1cccc(Nc2nc(Cl)ncc2F)c1
Agent: Nc1ccnc(N)n1
Product: Oc1cccc(Nc2nc(NCc3ccc4c(c3)OCCO4)ncc2F)c1

Procedure:
In a manner analogous to the preparation of 2-chloro-N4-(3,4-ethylenedioxyphenyl)-5-fluoro-N2-(3-hydroxyphenyl)-2,4-pyrimidineamine, 2-chloro-5-fluoro-N4-(3-hydroxyphenyl)-4-pyrimidineamine and 2,3-dihydro-1,4-benzodioxin-6-ylmethylamine gave N2-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-5-fluoro-N4-(3-hydroxyphenyl)-2,4:pyrimidinediamine. 1H NMR (CDCl3) δ 4.24 (s, 4H), 4.45 (d, J=6.0 Hz, 2H), 6.55 (ddd, J=0.9, 2.4 and 8.4 Hz, 1H), 6.66 (d, 1H), 6.84 (m, 4H), 6.90 (m, 1H), 7.14 (t, J=8.1 Hz, 1H), 7.30 (m, 1H), 7.86 (d, J=3.3 Hz, 1H); 19F NMR (282 MHz, CDCl3) δ −170.44; LCMS: ret. time: 18.33 min.; purity: 96.75%; MS (m/e): 369.03 (MH+).
Reaction SMILES: [CH3:1][C:2]([S:5]([NH2:7])=[O:6])([CH3:4])[CH3:3].[O:8]1[CH2:11][C:10](=O)[CH2:9]1>C1COCC1>[CH3:1][C:2]([S:5]([N:7]=[C:10]1[CH2:11][O:8][CH2:9]1)=[O:6])([CH3:4])[CH3:3]
Reactant: CC(C)(C)S(N)=O
Reactant: O=C1COC1
Solvent: C1CCOC1
Product: CC(C)(C)S(=O)N=C1COC1
Temperature: 60 °C
Reaction time: 18 h
Yield: 48 %

Procedure:
To a solution of 2-methyl-2-propanesulfinamide (1.47 g) and 3-oxetanone (0.85 mL) in THF (24 mL) was added Ti(OEt)4 (5.34 mL) dropwise over the course of 15 minutes at room temperature. After being stirred at 60° C. for 18 h, the reaction mixture was quenched by the rapid addition into ice cooled saturated sodium bicarbonate aqueous solution. The suspension was filtered through glass fiber filter paper and the cake was washed with ethyl acetate. The filtrate was washed with saturated sodium bicarbonate solution then brine. The organics were dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by column chromatography (10-100% ethyl acetate in hexanes) gave the product (1.02 g, 48%). 1HNMR (CDCl3) 400 MHz δ: 5.80 (ddd, J=15.6, 4.1, 2.3 Hz, 1H), 5.66 (ddd, J=15.6, 4.1, 2.3 Hz, 1H), 5.52-5.41 (m, 2H), 1.27 (s, 9H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1.[Li]C(C)(C)C.[CH3:14][O:15][C:16](=[O:28])[C:17]1[CH:26]=[CH:25][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:19][C:18]=1Br.CN1CCC(=C2C3C(=CC=CC=3)C=CC3C2=CC=CC=3)CC1>O1CCCC1.[Cl-].[Cl-].[Zn+2].Cl[Ni](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>[CH3:14][O:15][C:16](=[O:28])[C:17]1[CH:26]=[CH:25][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:19][C:18]=1[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1
Reactant: Cc1ccc(Br)cc1
Reactant: COC(=O)c1ccc(C(=O)OC)c(Br)c1
Agent: Cl[Ni](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CN1CCC(=C2c3ccccc3C=Cc3ccccc32)CC1
Agent: [Cl-]
Solvent: C1CCOC1
Product: COC(=O)c1ccc(C(=O)OC)c(-c2ccc(C)cc2)c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 85.3 %

Procedure:
4-Bromotoluene (6 g) was dissolved in tetrahydrofuran (20 ml). To this solution at -78° C. under N2 was added over a ten minute period, 1.7M tBuLi (42 ml). After two hours at room temperature, the reaction mixture was cooled to 0° C. and 1M ZnCl2 (36 ml) was added over a ten minute period. After one half hour at room temperature, bis(triphenylphosphine)nickel(II) chloride (1.32 g) was added followed by dimethyl-2-bromo-terepthalate (6 g) in tetrahydrofuran (20 ml) dropwise over a five minute period. The reactin mixture was stirred at room temperature for two hours. The tetrahydrofuran was removed under reduced pressure. The residue was treated with ethyl acetate and 1N HCl and the layers separated. The organic phase was washed with water, brine, dried over magnesium sulfate and evaporated gave the crude product. Chromatography on silica gel using 5% hexanes/methylene chloride gave the desired product (5.33 g).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]=[CH:11][C:10]=1[NH2:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:23][S:24](Cl)(=[O:26])=[O:25]>ClCCl>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]=[CH:11][C:10]=1[NH:15][S:24]([CH3:23])(=[O:26])=[O:25])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CS(=O)(=O)Cl
Reactant: Nc1cnccc1OCc1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)Nc1cnccc1OCc1ccccc1
Temperature: 25 °C

Procedure:
To a solution containing 4-(benzyloxy)pyridin-3-amine (6.2 g, 15.8 mmol), triethylamine (11 mL, 79 mmol), and dichloromethane (163 mL) was added methanesulfonylchloride (1.2 mL, 15.8 mmol) in dichloromethane (100 mL) drop wise over 90 min. The solution was maintained at room temperature for 6 h and concentrated to afford N-(4-(benzyloxy)pyridin-3-yl)methanesulfonamide which was used without further purification. LCMS: retention time: 1.305 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters-Xterra, 5 micron, C18, 4.6×30 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where solvent A was 5% CH3CN/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% CH3CN/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 279 (MH+).
Reaction SMILES: [CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[O:13])[C:10]([OH:12])=[O:11])[N:8]=1)=[O:2].C(=O)(O)[O-].[Na+].C(O)C.[BH4-].[Na+]>O>[OH:13][CH:9]([C:7]1[N:8]=[C:4]([NH:3][CH:1]=[O:2])[S:5][CH:6]=1)[C:10]([OH:12])=[O:11]
Reactant: O=CNc1nc(C(=O)C(=O)O)cs1
Agent: O=C([O-])O
Agent: O=CN=c1[nH]c(C(=O)C(=O)O)cs1
Agent: [BH4-]
Solvent: CCO
Solvent: O
Product: O=CNc1nc(C(O)C(=O)O)cs1
Reaction time: 8 h

Procedure:
To a suspension of 2-(2-formylaminothiazol-4-yl)glyoxylic acid, which can be represented as 2-(2-formylimino-2,3-dihydrothiazol-4-yl)glyoxylic acid, (20 g.) in water (400 ml.) was added sodium bicarbonate (8.4 g.) under ice-cooling and stirring, and the mixture was stirred for 10 minutes at the same temperature, and then ethanol (10 ml.) was added thereto. To the mixture was added sodium borohydride (1.52 g.) over 10 minutes with stirring at the same temperature, and the mixture was stirred for 1 hour and 50 minutes at the same temperature. After the reaction, the reaction mixture was filtered. The filtrate was adjusted to pH 4.0 with 10% hydrochloric acid and then concentrated under reduced pressure till the volume became 100 ml. The concentrated filtrate was adjusted to pH 1 with 10% hydrochloric acid, and crystallization was induced by scratching. The concentrated filtrate was stirred for 1 hour at room temperature and then allowed to stand overnight in a refrigerator. The precipitates were collected by filtration, washed with ice-water twice and then dried under suction to give 2-hydroxy-2-(2-formylaminothiazol-4-yl)acetic acid, which can be represented as 2-hydroxy-2-(2-formylimino-2,3-dihydrothiazol-4-yl)acetic acid, (14.8 g.), mp. 188° to 189° C. (dec.).
Reaction SMILES: [C:1]([O:5]O)([CH3:4])(C)C.[Cl-].[Na+].[C:9]([O:32][CH:33]1[CH2:38][C:37]([CH3:40])([CH3:39])[NH:36][C:35]([CH3:42])([CH3:41])[CH2:34]1)(=[O:31])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH:21]1[CH2:26][C:25]([CH3:28])([CH3:27])[NH:24][C:23]([CH3:30])([CH3:29])[CH2:22]1)=[O:19]>CCCCCCCCC.C/C(/O)=C/C(C)=O.C/C(/O)=C/C(C)=O.C/C(/O)=C/C(C)=O.[V]>[C:9]([O:32][CH:33]1[CH2:38][C:37]([CH3:40])([CH3:39])[N:36]([O:5][CH2:1][CH2:4][CH2:27][CH2:25][CH2:26][CH2:21][CH2:22][CH2:23][CH3:29])[C:35]([CH3:42])([CH3:41])[CH2:34]1)(=[O:31])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH:21]1[CH2:26][C:25]([CH3:27])([CH3:28])[N:24]([O:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH3:10])[C:23]([CH3:29])([CH3:30])[CH2:22]1)=[O:19]
Reactant: CC(C)(C)OO
Reactant: CC1(C)CC(OC(=O)CCCCCCCCC(=O)OC2CC(C)(C)NC(C)(C)C2)CC(C)(C)N1
Agent: [V]
Agent: CC(=O)/C=C(/C)O
Agent: [Cl-]
Solvent: CCCCCCCCC
Product: CCCCCCCCCON1C(C)(C)CC(OC(=O)CCCCCCCCC(=O)OC2CC(C)(C)N(OCCCCCCCCC)C(C)(C)C2)CC1(C)C
Temperature: 151 °C
Yield: 7.9 %

Procedure:
A 2-phase mixture of 85.7 g (0.666 mol) of 70% aqueous tert-butyl hydroperoxide, 200 ml of n-nonane and 10 g of sodium chloride is agitated in a separatory funnel. The organic layer is dried over anhydrous magnesium sulfate. A mixture of 40.0 g (0.0832 mol) of bis-(2,2,6,6-tetramethylpiperidin-4-yl) sebacate and the tert-butyl hydroperoxide solution in n-nonane is heated to reflux (151° C.) under a nitrogen atmosphere. Vanadium (III) acetylacetonate (2.0 g) is added over a 15-minute interval. The reaction mixture is diluted with 50 ml of nonane. The reaction mixture is heated at reflux for 22 hours. Water is collected in a Dean-Stark trap. The mixture turns red and then darkens in color. The solvent is then removed under reduced pressure. The residue is dissolved in 150 ml of heptane and then passed through a short column of silica gel with additional heptane. The crude product is purified by chromatography (Waters Prep 500A HPLC; 29:1 heptane:ethyl acetate) to afford 2.5 g (4% yield) of the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]#[CH:12])[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.I[C:14]1[CH:19]=[CH:18][C:17]([C:20]#[C:21][Si:22]([CH3:25])([CH3:24])[CH3:23])=[CH:16][CH:15]=1>C1COCC1.C(N(CC)CC)C.[Cu]I.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[CH3:23][Si:22]([C:21]#[C:20][C:17]1[CH:18]=[CH:19][C:14]([C:12]#[C:11][C:5]2[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=[C:3]([O:2][CH3:1])[CH:4]=2)=[CH:15][CH:16]=1)([CH3:24])[CH3:25]
Reactant: C[Si](C)(C)C#Cc1ccc(I)cc1
Reactant: C#Cc1cc(OC)cc(OC)c1
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COc1cc(C#Cc2ccc(C#C[Si](C)(C)C)cc2)cc(OC)c1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 90.5 %

Procedure:
Into a 100 ml round bottom flask was placed a mixture of 1.31 g (0.0081 mole) of 3.5-dimethoxyphenylacetylene, 2.25 g (0.0075 mole) of 4-iodophenyl-trimethylsilylacetylene, 0.016 g (0.084 mmole) of CuI, 0.155 g (0.22 mmole) of bis(triphenylphosphine)palladium(II)dichloride in 15 ml of THF and 15 ml of triethylamine. The light brown solution turned to a suspension within a minute. After ˜40 min, the reaction mixture turned to an orange solution with some white ppt. The reaction was followed by TLC. The mixture was stirred at room temperature under nitrogen overnight. TLC showed presence of staring material still. The reaction was stirred continuously overnight at room temp. Not much further reaction had occurred. It was then stirred overnight at 50° C. TLC indicated that only a trace of starting material was present. The reaction was then terminated and the reaction mixture was filtered and the filtrate concentrated under reduced pressure. The residue was redissolved in 15 ml of chloroform and the solution was washed two times with water (15 ml each) and dried over anhydrous MgSO4, filtered and concentrated. 2.27 g (90.4% yield) of solid was obtained. 1HNMR: 0.26 ppm (s, 9H); 3.83 ppm (s, 6H); 6.49 ppm (s, 1H); 6.70 ppm (s, 2H); 7.47 ppm (s, 4H).
Reaction SMILES: FC1C=CC(C(C2C=CC(F)=CC=2)=O)=CC=1.OC1C=CC(C2C=CC(O)=CC=2)=CC=1.C(=O)([O-])[O-].[K+].[K+].[N+]([C:40]1[CH:41]=[C:42]([C:48]#[N:49])[C:43](=[CH:46][CH:47]=1)[C:44]#[N:45])([O-])=O>O.C1(C)C=CC=CC=1.CC(N(C)C)=O>[C:48](#[N:49])[C:42]1[C:43](=[CH:46][CH:47]=[CH:40][CH:41]=1)[C:44]#[N:45]
Reactant: N#Cc1ccc([N+](=O)[O-])cc1C#N
Agent: O=C([O-])[O-]
Agent: O=C(c1ccc(F)cc1)c1ccc(F)cc1
Agent: Oc1ccc(-c2ccc(O)cc2)cc1
Solvent: O
Solvent: CC(=O)N(C)C
Solvent: Cc1ccccc1
Product: N#Cc1ccccc1C#N
Temperature: 160 °C
Yield: 568.9 %

Procedure:
To a 100 ml, 3-necked flask equipped with a thermometer and a Dean-Stark trap was added 3.52 gm (16.1 mmol) of 4,4'-difluorobenzophenone, 4.0 gm (21.5 mmol) of 4,4'-dihydroxybiphenyl, and 40 ml of dimethylacetamide (DMAC). After flushing the mixture for 30 minutes with dry nitrogen, 5.0 gm (36.2 mmol) of pulverized anhydrous potassium carbonate was added with stirring. The reaction content was stirred at 90° C. for 1 hour. Toluene was added to the Dean-Stark trap and to the reaction vessel (4 ml). The reaction mixture was refluxed at 145°-150° C. for 10 hours. Water which formed as a by-product was removed by azeotropic distillation. The toluene was removed by distillation while heating to 160° C. Upon cooling to ambient condition, 1.86 gm (10.7 mmol) of 4-nitrophthalonitrile was added. The reaction mixture turned purple. The reaction content was then stirred at the ambient temperature for 2 hours and at 90° C. for 6 hours. The reaction was monitored by FTIR spectroscopy and showed the complete disappearance of the absorptions attributed to the nitro and hydroxyl groups. The room temperature mixture was poured into 200 ml of water with stirring. The solid precipitate was collected by suction filtration, washed exhaustively with water, and dried to afford 7.8 gm of oligomeric phthalonitrile monomer.
Reaction SMILES: OC1C=CC(C(C2C=CC(O)=CC=2)(C)C)=CC=1.ClCCOCCCl.C([O-])([O-])=O.[K+].[K+].[N+]([C:34]1[CH:35]=[C:36]([C:42]#[N:43])[C:37](=[CH:40][CH:41]=1)[C:38]#[N:39])([O-])=O.Cl>O.CS(C)=O>[C:42](#[N:43])[C:36]1[C:37](=[CH:40][CH:41]=[CH:34][CH:35]=1)[C:38]#[N:39]
Reactant: N#Cc1ccc([N+](=O)[O-])cc1C#N
Agent: CC(C)(c1ccc(O)cc1)c1ccc(O)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: ClCCOCCCl
Solvent: CS(C)=O
Solvent: O
Product: N#Cc1ccccc1C#N
Temperature: 90 °C

Procedure:
To a 2000 mL, three-necked flask fitted with a thermometer and a nitrogen inlet were added bisphenol A (100 g, 0.298 mol), bis(2-chloroethyl) ether (31.3 g, 0.219 mol), powdered anhydrous K2CO3 (150 g, 1.09 mol), and dimethylsulfoxide (DMSO) (1000 mL). The resulting mixture was degassed with nitrogen at ambient temperature and heated at 90° C. under a nitrogen atmosphere for 8-16 hr. The mixture was cooled to 50° C. At this time, 4-nitrophthalonitrile (77.7 g, o.449 mol) was added in one portion and the reaction mixture was heated at 80° C. for 6-8 hr. The mixture was allowed to cool to ambient temperature and poured into 1000 mL of distilled water. The mixture was made acidic by the addition of 6 M aqueous HCl and the resin was extracted out of the water layer by toluene (200 mL). The toluene extracts were washed 3 times with 500 mL of distilled water and dried using magnesium sulfate. Removal of the toluene resulted in an amber oil, which was dried at 80° C. under vacuum. The 2:1 oligomeric phthalonitrile was isolated as an amber glassy solid (164 g, 94%). 1H-NMR [CDCl3]: λ 7.68 (m, aromatic-HR), 7.27 (m, aromatic-HR), 7.11 (m, aromatic-HR), 6.97 (m, aromatic-HR), 6.81 (m, aromatic-HR), 4.10 (m, aliphatic-HR), 3.88 (m, aliphatic-HR), 1.73 (s, aliphatic-HR), 1.66 (s, aliphatic-HR), 1.59 (s, aliphatic-HR).
Reaction SMILES: [CH3:1][C:2]([CH3:8])([CH2:5][CH2:6][OH:7])[CH2:3][OH:4].N1C=CN=C1.[Si:14](Cl)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]>C1COCC1>[Si:14]([O:7][CH2:6][CH2:5][C:2]([CH3:8])([CH3:1])[CH2:3][OH:4])([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: CC(C)(CO)CCO
Agent: c1c[nH]cn1
Solvent: C1CCOC1
Product: CC(C)(CO)CCO[Si](C)(C)C(C)(C)C
Reaction time: 16 h
Yield: 73.3 %

Procedure:
To a solution of the product from Example 9A (0.80 g, 6.8 mmol) and imidazole (0.462 g) in THF (8.0 mL) at room temperature was added tert-butyldimethylsilyl chloride (1.02 g), and the solution was stirred for 16 hours. The reaction mixture was partitioned between ethyl acetate and water, and the organic was washed with brine, dried over MgSO4, filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with a gradient starting with 33% hexanes in chloroform and ending with 25% ethyl acetate in chloroform, to give the title compound (1.153 g, 73%).
Reaction SMILES: [Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:10][CH3:11])=[C:5]([Cl:12])[C:4]=1[F:13].[B:14](OC)([O:17]C)[O:15]C.C(OCC)(=O)C>C1COCC1.Cl>[Cl:12][C:5]1[C:4]([F:13])=[C:3]([B:14]([OH:17])[OH:15])[CH:8]=[CH:7][C:6]=1[O:9][CH2:10][CH3:11]
Reactant: COB(OC)OC
Reactant: CCOc1ccc(Br)c(F)c1Cl
Agent: Cl
Agent: [Mg]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCOc1ccc(B(O)O)c(F)c1Cl
Temperature: 50 °C
Reaction time: 1 h
Yield: 83.3 %

Procedure:
4.79 g of well dried magnesium and 50 mL of THF were placed in a reactor under nitrogen atmosphere, and heated to 50° C. 50.0 g of the compound (1) dissolved in 200 mL of THF was added dropwise thereto at a temperature range of from 43 to 48° C. over 60 minutes, followed by stirring for 60 minutes. The reaction mixture was cooled to 25° C. Thereafter, the resulting reaction mixture was added dropwise to a solution of 24.6 g of trimethyl borate and 100 mL of THF having been cooled to −50° C. in a nitrogen atmosphere at a temperature range of from −60 to −40° C. over 60 minutes. The reaction mixture was warmed to 0° C. and then put in 400 mL of 3N hydrochloric acid at 0° C. 700 mL of ethyl acetate was added to and mixed with the resulting solution, and separated into an organic layer and an aqueous layer by standing still, so as to attain extraction to the organic layer. The resulting organic layer was fractionated and washed with a saturated sodium bicarbonate aqueous solution and water, followed by drying over anhydrous magnesium sulfate. Thereafter, the solvent was removed by distillation under reduced pressure to obtain a residue. The residue was recrystallized from heptane. The recrystallization operation was again repeated to obtain 35.9 g of 3-chloro-4-ethoxy-2-fluorophenylboronic acid (12). The resulting compound (12) was a pale yellow solid matter.
Reaction SMILES: C(Cl)Cl.[Br:4][C:5]1[CH:13]=[CH:12][C:8]([CH2:9][CH2:10][OH:11])=[CH:7][CH:6]=1.[O:14]1[CH:19]=[CH:18][CH2:17][CH2:16][CH2:15]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CCOC(C)=O>[Br:4][C:5]1[CH:13]=[CH:12][C:8]([CH2:9][CH2:10][O:11][CH:15]2[CH2:16][CH2:17][CH2:18][CH2:19][O:14]2)=[CH:7][CH:6]=1
Reactant: OCCc1ccc(Br)cc1
Reactant: C1=COCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: O
Product: Brc1ccc(CCOC2CCCCO2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Into 30 mL of CH2Cl2 in a 150 mL RB flask was dissolved 4-bromophenethyl alcohol (7.00 g, 34.80 mmol) and 3,4-dihydro-2H-pyran (3.80 mL, 41.61 mmol). To this solution was added a few crystals of p-toluenesulfonic acid monohydrate. The reaction mixture was then stirred at room temperature under a blanket of nitrogen overnight. Overnight the reaction mixture changed colour again to a deep brown colour. The reaction mixture was transferred to a 250 mL separating funnel and extracted with 150 mL of saturated NaHCO3(aq) solution during which time the brown colouration in the organic layer faded to an orange colour. The layers were separated and the organic layer was extracted again with 150 mL of brine. The organic layer was then separated and dried over anhydrous MgSO4 for 1 hour at room temperature. The mixture was then filtered and the collected solid washed with 3×30 mL portions of CH2Cl2. The filtrate and washings were combined and stripped to dryness on a rotary evaporator to yield an orange oil. Column chromatographic conditions for the remainder of the crude product were determined by TLC analysis (10% EtOAc/90% n-hexane eluant) which indicated a major spot at Rf 0.5 with a few minor spots on and around the baseline. The crude product was then purified by dry column flash chromatography using a sinter of 80 mm diameter and 80 mm depth packed to a depth of 5.5 cm with Merck 60 (15-40 μm) silica gel, time per fraction: 4.00 minutes, crude product pre-loaded onto 12.5 g of Merck 60 (15-40 □m) and this loaded on top of the column. n-Hexane/EtOAc elution in 100 mL fractions with the EtOAc component increasing in 1% increments from 0% (fraction 1) to 15% (fraction 16). Fractions' 9 & 10 “foamed” on leaving the column and TLC (10% EtOAc/90% n-hexane) of fractions' 8-15 indicated pure product was contained in fractions' 9-12 and these were combined and stripped to dryness on a rotary evaporator before being further dried in vacuo (oil immersion pump) overnight at room temperature. Yield: 9.821 g (98.9%, colourless liquid). 1H NMR (CDCl3) δ 1.40-1.88 (m, 6H, [3×—CH2—]pyran), 2.86 (t, 2H, ArCH2—), 3.45 (m, 1H, [OCHaHb-]pyran), 3.58 (q, 1H, —OpyranCHaHb—), 3.73 (m, 1H, [OCHaHb-]pyran), 3.92 (q, 1H, —OpyranCHaHb—), 4.57 (m, 1H, [—OCHO-]pyran), 7.10 (d, 2H, ArH), 7.40 (d, 2H, ArH).