Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[N:10]=[C:9]([CH2:11][N:12]3[CH2:17][CH2:16][N:15]([S:18]([CH3:21])(=[O:20])=[O:19])[CH2:14][CH2:13]3)[S:8][C:6]=2[N:7]=1.B(O)(O)[C:29]1[CH:37]=[CH:36][CH:35]=[C:34]2[C:30]=1[CH:31]=[N:32][NH:33]2.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(#N)C>[NH:33]1[C:34]2[C:30](=[C:29]([C:2]3[N:3]=[C:4]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[C:5]4[N:10]=[C:9]([CH2:11][N:12]5[CH2:17][CH2:16][N:15]([S:18]([CH3:21])(=[O:20])=[O:19])[CH2:14][CH2:13]5)[S:8][C:6]=4[N:7]=3)[CH:37]=[CH:36][CH:35]=2)[CH:31]=[N:32]1
Reactant: OB(O)c1cccc2[nH]ncc12
Reactant: CS(=O)(=O)N1CCN(Cc2nc3c(N4CCOCC4)nc(Cl)nc3s2)CC1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Product: CS(=O)(=O)N1CCN(Cc2nc3c(N4CCOCC4)nc(-c4cccc5[nH]ncc45)nc3s2)CC1

Procedure:
5-Chloro-2-((4-methylsulfonylpiperazin-1-yl)methyl)-7-morpholinothiazolo[5,4-d]pyrimidine, 1H-indazol-4-yl-4-boronic acid (1.2 eq), and trans-dichlorobis(triphenylphosphine)palladium(II) (0.1 eq) were combined in a solution of equal parts sodium carbonate aqueous solution (1M, 3 eq) and acetonitrile. The solution was microwaved at 130° C. for eighteen minutes. An additional 0.1 equivalents of trans-dichlorobis(triphenylphosphine)palladium(II) was added and the solution was microwaved at 130° C. for an additional twenty minutes. Acetonitrile was added and the solution was filtered. The organic layer was purified by reverse phase chromatography to give the off white solid of 129.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C:15]3[CH:24]=[CH:23][C:18]([C:19]([O:21]C)=[O:20])=[CH:17][CH:16]=3)[N:8]=2)[CH:2]=1.O[Li].O.Cl>C1COCC1.CO.O>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][CH2:14][C:15]3[CH:16]=[CH:17][C:18]([C:19]([OH:21])=[O:20])=[CH:23][CH:24]=3)[N:8]=2)[CH:2]=1
Reactant: COC(=O)c1ccc(CNc2nccc(-c3cccnc3)n2)cc1
Agent: Cl
Agent: [Li]O
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: O=C(O)c1ccc(CNc2nccc(-c3cccnc3)n2)cc1
Temperature: 40 °C
Reaction time: 8 h
Yield: 97.7 %

Procedure:
To a stirred solution of 41 (3.68 g, 11.5 mmol) in a mixture of THF (23 ml) and MeOH (23 ml) was added a solution of LiOH—H2O (1.06 g, 25.3 mmol) in water (11.5 ml) at room temperature. The reaction mixture was stirred at 40° C. overnight, cooled to the room temperature, and an aqueous solution of HCl (12.8 ml, 2N) was added (pH˜4-5). The mixture was concentrated to dryness; the formed solid was triturated with water, filtered off, washed with minimum H2O and dried to afford the title compound 42 (3.44 g, 95%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ(ppm): 12.83 (bs, 1H), 9.23 (bs, 1H), 8.73-8.66 (m, 1H) 8.46-8.36 [m, included at 8.42 (d, J=5.1 Hz), 2H], 8.02 (t, J=6.3 Hz, 1H), 7.91 (d, J=8.2 Hz, 2H), 7.60-7.40 (m, 3H), 7.28 (d, J=5.1 Hz, 1H), 4.67 (d, J=6.3 Hz, 2H).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([CH2:10][CH2:11][O:12][CH2:13][C:14](O)=O)[CH:8]=[CH:9][C:2]1=2.C(Cl)(=O)C(Cl)=O.[NH2:23][CH:24]([CH2:26][OH:27])[CH3:25].Cl>C(Cl)Cl.O1CCCC1.C(N(CC)CC)C.CN(C)C=O>[S:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[C:7]([CH2:10][CH2:11][O:12][CH2:13][CH2:14][NH:23][CH:24]([CH3:25])[CH2:26][OH:27])[CH:8]=[CH:9][C:2]1=2
Reactant: CC(N)CO
Reactant: O=C(O)COCCc1ccc2sccc2c1
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: C1CCOC1
Product: CC(CO)NCCOCCc1ccc2sccc2c1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
In 10 mL of methylene chloride is dissolved 1.0 g of 2-(2-benzo[b]thiophen-5-ylethoxy)-acetic acid. At an ice-cooled temperature, 0.41 mL of oxalyl chloride and 0.1 mL of N,N-dimethylformamide are added to the solution obtained above, and the mixture is stirred at ambient temperature for 1.5 hours. After cooling the mixture to −50° C., 0.41 mL of DL-alaninol and 1.77 mL of triethylamine are dropwise added, and the mixture thus formed is stirred at ambient temperature for 4 hours. Ice water is added to the reaction mixture, pH is adjusted to 1 with 6 mol/L hydrochloric acid, and the organic layer is separated. The organic layer is washed with saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. The residue thus obtained is dissolved in 10 mL of tetrahydrofuran and cooled with ice, to which is dropwise added 16.9 mL of 1 mol/L solution of borane-tetrahydrofuran complex in tetrahydrofuran. The mixture thus obtained is stirred at ambient temperature for 13 hours. The reaction mixture is acidified with 5.6 mL of 6 mol/L hydrochloric acid and heated under reflux for one hour. After cooling the reaction mixture, the solvent is distilled off under reduced pressure, water and ethyl acetate are added to the residue, and the aqueous layer is separated. Ethyl acetate is added to the aqueous layer, pH is adjusted to 9.5 with 50% aqueous solution of sodium hydroxide, and the organic layer is separated. The organic layer thus obtained is washed with saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, the solvent is distilled off under reduced pressure, and an oily residue thus obtained is purified by column chromatography (eluent: chloroform:methanol=40:1 to 30:1) to obtain 0.80 g of 2-{[2-(2-benzo[b]thiophen-5-ylethoxy)ethyl]amino}-1-propanol as a light yellow-colored oily product.
Reaction SMILES: [CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:17])[CH2:15][CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:28]([O:35][C:36]1[CH:41]=[CH:40][C:39]([CH2:42]Br)=[CH:38][CH:37]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.O1CCNC1=O>O1CCCC1>[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:17])[C@H:15]([CH3:16])[CH2:42][C:39]1[CH:40]=[CH:41][C:36]([O:35][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:37][CH:38]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: BrCc1ccc(OCc2ccccc2)cc1
Reactant: CCC(=O)N1C(=O)OC[C@H]1Cc1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: O=C1NCCO1
Agent: [Na+]
Solvent: C1CCOC1
Product: C[C@H](Cc1ccc(OCc2ccccc2)cc1)C(=O)N1C(=O)OC[C@H]1Cc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of (R)-4-benzyl-3-propionyloxazolidin-2-one (17.0 g, 72.8 mmol) in tetrahydrofuran (200 mL) at −78° C. was added sodium bis(trimethylsilyl)amide (80 mL, 79.4 mmol) and stirred for 1 hour. A solution of 1-(benzyloxy)-4-(bromomethyl)benzene (746) (20.0 g, 72.2 mmol) in tetrahydrofuran (50 mL) was added slowly to the oxazolidinone solution at −78° C. and allowed to warm to room temperature overnight. The solvent was removed in vacuo and the residue was dissolved with ethyl acetate. The organic layer was washed with water, brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (20%) to afford (R)-4-benzyl-3-((R)-3-(4-(benzyloxy)phenyl)-2-methylpropanoyl)oxazolidin-2-one (747).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[Br:18]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>>[Br:18][CH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:11]=1)[C:5]([O:7][CH3:8])=[O:6]
Reactant: O=C1CCC(=O)N1Br
Reactant: COC(=O)c1cc(C)cc(-c2ccccc2)c1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Product: COC(=O)c1cc(CBr)cc(-c2ccccc2)c1
Yield: 80 %

Procedure:
A solution of methyl 3-methyl-5-phenylbenzoate (3.5 g; 15.6 mmol); N-bromosuccinimide (2.78 g; 15.6 mmol), 2,2′-azobis(2′-methylpropionitrile) (0.12 g; 0.72 mmol) and benzoylperoxide (0.12 g; 0.48 mmol) in tetrachloroamethane (120 ml) was heated at reflux for 5 hours. After evaporation to dryness, the residue was purified by flash chromatography eluting with petroleum ether/ethyl acetate (97/3) to give methyl 3-bromomethyl-5-phenylbenzoate as a solid. Yield=80%.
Reaction SMILES: [CH:1]1([C:4]2[CH:5]=[CH:6][C:7]([C:15]([OH:17])=O)=[N:8][C:9]=2[O:10][CH2:11][CH:12]2[CH2:14][CH2:13]2)[CH2:3][CH2:2]1.[NH2:18][C@@H:19]([CH2:24][CH:25]1[CH2:27][CH2:26]1)[C:20]([CH3:23])([OH:22])[CH3:21]>>[CH:25]1([CH2:24][C@H:19]([NH:18][C:15]([C:7]2[CH:6]=[CH:5][C:4]([CH:1]3[CH2:2][CH2:3]3)=[C:9]([O:10][CH2:11][CH:12]3[CH2:13][CH2:14]3)[N:8]=2)=[O:17])[C:20]([OH:22])([CH3:23])[CH3:21])[CH2:27][CH2:26]1
Reactant: CC(C)(O)[C@@H](N)CC1CC1
Reactant: O=C(O)c1ccc(C2CC2)c(OCC2CC2)n1
Product: CC(C)(O)[C@H](CC1CC1)NC(=O)c1ccc(C2CC2)c(OCC2CC2)n1

Procedure:
The title compound was synthesized in analogy to Example 1, using 5-cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid (Example 42 a) and (S)-3-amino-4-cyclopropyl-2-methyl-butan-2-ol (Example 135 c) as starting materials, MS (EI): m/e=359.2 [M+H]+.
Reaction SMILES: [C:1]([O:4][CH:5]([CH2:9][O:10][S:11]([C:14]1[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=1)(=[O:13])=[O:12])[CH2:6][C:7]#[N:8])(=[O:3])[CH3:2]>C(Cl)(Cl)Cl>[C:1]([O:4][C@@H:5]([CH2:9][O:10][S:11]([C:14]1[CH:20]=[CH:19][C:17]([CH3:18])=[CH:16][CH:15]=1)(=[O:13])=[O:12])[CH2:6][C:7]#[N:8])(=[O:3])[CH3:2]
Reactant: CC(=O)OC(CC#N)COS(=O)(=O)c1ccc(C)cc1
Solvent: ClC(Cl)Cl
Product: CC(=O)O[C@H](CC#N)COS(=O)(=O)c1ccc(C)cc1
Yield: 46 %

Procedure:
[α]28D=+22.6 (c 1.0, CHCl3); NMR and Mass spectral data are identical to 3-acetyloxy-4-tosyloxybutanenitrile; Yield 46%.
Reaction SMILES: Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([CH2:12][CH3:13])(=[O:11])=[O:10])=[CH:5][CH:4]=1.[OH-].[NH4+:15]>CO>[CH2:12]([S:9]([C:6]1[CH:7]=[CH:8][C:3]([CH2:2][NH2:15])=[CH:4][CH:5]=1)(=[O:11])=[O:10])[CH3:13]
Reactant: CCS(=O)(=O)c1ccc(CBr)cc1
Reactant: [NH4+]
Agent: [OH-]
Solvent: CO
Product: CCS(=O)(=O)c1ccc(CN)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 30 %

Procedure:
To a solution of 1-(bromomethyl)-4-(ethylsulfonyl)benzene (6.62 g, 25.2 mmol) in MeOH (30 mL) was added 28% aqueous ammonium hydroxide solution (30 mL). The mixture was stirred at rt overnight. The mixture was then concentrated under reduced pressure. The residue was purified by basic preparative HPLC separation to afford (4-(ethylsulfonyl)phenyl)methanamine (1.5 g, 30%) as a yellow solid. LC-MS tR=1.747 min in 0-30CD—3 min chromatography (Durashell C18, 2.1*30 mm, 3 um), MS (ESI) m/z 200.0 [M+H]+ and 399.0 [2M+H]+. 1H NMR (CDCl3, 400 MHz): δ 7.85 (d, J=8.0 Hz, 2H), 7.53 (d, J=8.0 Hz, 2H), 3.98 (s, 2H), 3.10 (q, J=7.6 Hz, 2H), 1.26 (t, J=7.6 Hz, 3H). Preparative Basic HPLC Method mobile phase A: water with 0.05% NH3H2O solution; mobile phase B: MeCN; flow rate: 30 mL/min; detection: UV 220 nm/254 nm; column: Synergi 200 mm×25 mm×5 μm; column temperature: 30° C.
Reaction SMILES: Cl.[F:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)[C:6](O)=O.FC1C=[C:24](C=CC=1OCCN1CCCCC1)[CH2:25][NH:26][C:27]1[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[CH:29][C:28]=1[C:35]1[CH:44]=[CH:43][C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH:36]=1>>[CH2:25]([N:26]([CH2:6][C:5]1[CH:9]=[CH:10][C:11]([O:12][CH2:13][CH2:14][N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)=[C:3]([F:2])[CH:4]=1)[C:27]1[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[CH:29][C:28]=1[C:35]1[CH:44]=[CH:43][C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH:36]=1)[CH3:24]
Reactant: O=C(O)c1ccc(OCCN2CCCCC2)c(F)c1
Reactant: COc1ccc(-c2ccc3ccccc3c2)c(NCc2ccc(OCCN3CCCCC3)c(F)c2)c1
Agent: Cl
Product: CCN(Cc1ccc(OCCN2CCCCC2)c(F)c1)c1cc(OC)ccc1-c1ccc2ccccc2c1

Procedure:
Synthesized from 5-methoxy-2-naphthalen-2-ylamine and 3-fluoro-4-(2-piperidin-1-ylethoxy)benzoic acid hydrochloride according to an analogous synthetic method to Example 114, [3-fluoro-4-(2-piperidin-1-ylethoxy)benzyl](5-methoxy-2-naphthalen-2-ylphenyl)amine (290 mg) was used according to an analogous synthetic method to Example 36 to provide ethyl[3-fluoro-4-(2-piperidin-1-ylethoxy)benzyl](5-methoxy-2-naphthalen-2-ylphenyl)amine (252 mg). This compound (250 mg) was used according to an analogous synthetic method to Example 111 to provide the title compound (222 mg).
Reaction SMILES: Cl.[O:2]=[C:3]1[N:7]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=2)[CH2:6][C:5]2([CH2:22][CH2:21][NH:20][CH2:19][CH2:18]2)[O:4]1.[Br:23][C:24]1[CH:25]=[C:26]([CH:29]=[C:30]([Cl:32])[CH:31]=1)[CH:27]=O>>[Br:23][C:24]1[CH:25]=[C:26]([CH:29]=[C:30]([Cl:32])[CH:31]=1)[CH2:27][N:20]1[CH2:21][CH2:22][C:5]2([O:4][C:3](=[O:2])[N:7]([C:8]3[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][CH:9]=3)[CH2:6]2)[CH2:18][CH2:19]1
Reactant: O=Cc1cc(Cl)cc(Br)c1
Reactant: COC(=O)c1ccc(N2CC3(CCNCC3)OC2=O)cc1
Agent: Cl
Product: COC(=O)c1ccc(N2CC3(CCN(Cc4cc(Cl)cc(Br)c4)CC3)OC2=O)cc1

Procedure:
The title compound was prepared from methyl 4-(2-oxo-1-oxa-3,8-diazaspiro[4.5]dec-3-yl)benzoate hydrochloride salt (50 mg, 0.153 mmol; Example 1, Step 2) and 3-bromo-5-chlorobenzaldehyde (43.7 mg, 0.199 mmol) following essentially the same procedure described in Step 1 of Example 7-6. The title compound was obtained as a yellow oil (76 mg) that was used without any further purification.
Reaction SMILES: [CH2:1]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH:19]([S:24][CH2:25][CH2:26][C:27]1[NH:31][N:30]=[N:29][N:28]=1)[C:20]([O:22]C)=[O:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[OH-].[Na+]>CO.O>[CH2:1]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH:19]([S:24][CH2:25][CH2:26][C:27]1[NH:31][N:30]=[N:29][N:28]=1)[C:20]([OH:22])=[O:21])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCCc1ccccc1C(SCCc1nnn[nH]1)C(=O)OC
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CCCCCCCCCCCCc1ccccc1C(SCCc1nnn[nH]1)C(=O)O
Reaction time: 0.5 h
Yield: 74.9 %

Procedure:
A stirred suspension of methyl 2-(2-dodecylphenyl)-2-[2-(tetrazol-5-yl)ethylthio]acetate (0.57 g, 1.28 mmol) in 10 ml of methanol and 8 ml of water at 70° was treated with 3 ml of 2.5N sodium hydroxide. After 30 minutes at 70°, the mixture was cooled, diluted with 10 ml of water and filtered. The filtrate was acidified, extracted with ethyl acetate, and the extracts were dried and the solvente evaporated. The residue was recrystallized from methanol and gave the desired product 0.415 g (74%). NMR (CDCl3 /Me2CO): 10.23-11.70 (broad, 2H), 7.52-7.62 (m,1H), 7.27 (s,3H), 5.04 (s,1H), 3.0-3.44 (m,4H), 2.63-2.92 (t,2H), 1.12-1.84 (m,20H), 0.62-1.02 (t,3H).
Reaction SMILES: [C:1]([C:4]1[O:5][C:6]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][C:7]=2[N:8]=1)([OH:3])=[O:2].[CH2:14](O)[CH2:15][CH3:16]>S(=O)(=O)(O)O>[CH2:14]([O:2][C:1]([C:4]1[O:5][C:6]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][C:7]=2[N:8]=1)=[O:3])[CH2:15][CH3:16]
Reactant: CCCO
Reactant: O=C(O)c1nc2cc(O)ccc2o1
Agent: O=S(=O)(O)O
Product: CCCOC(=O)c1nc2cc(O)ccc2o1

Procedure:
12.72 g (49.2 mmoles) of 2-carboxy-5-hydroxybenzoxazole is dissolved in 200 ml of n-propanol and 1 drop of concentrated sulfuric acid is added. The mixture is refluxed for 30 hours, concentrated. The resulting solid is suspended in water, neutralized with sodium bicarbonate and filtered, washing the solid with water, then drying. This gives n-propyl-5-hydroxybenzoxazole-2carboxylate which is purified by recrystallization from n-propanol/acetone or by HPLC.
Reaction SMILES: C(O[C@@H:5]1[O:20][C@H:19]([CH2:21][O:22][C:23](=[O:25])[CH3:24])[C@@H:14]([O:15][C:16](=[O:18])[CH3:17])[C@H:11]([O:12][CH3:13])[C@H:6]1[O:7][C:8](=[O:10])[CH3:9])(=O)C.[CH2:26]([SH:28])[CH3:27].B(F)(F)F.CCOCC.C(=O)([O-])O.[Na+]>C1(C)C=CC=CC=1>[C:8]([O:7][C@@H:6]1[C@@H:11]([O:12][CH3:13])[C@H:14]([O:15][C:16](=[O:18])[CH3:17])[C@@H:19]([CH2:21][O:22][C:23](=[O:25])[CH3:24])[O:20][C@H:5]1[S:28][CH2:26][CH3:27])(=[O:10])[CH3:9]
Reactant: CO[C@@H]1[C@@H](OC(C)=O)[C@H](OC(C)=O)O[C@H](COC(C)=O)[C@H]1OC(C)=O
Reactant: CCS
Agent: FB(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: CCS[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC)[C@H]1OC(C)=O
Yield: 53438.8 %

Procedure:
1,2,4,6-Tetra-O-acetyl-3-O-methyl-β-D-glucopyranose 1 (69 g, 0.19 mmol), (B. Helferich et al., J. prakt. Chem., 132, 321 (1932)) is dissolved in toluene (580 ml). Ethanethiol (28 ml, 0.38 mmol) is added, followed by dropwise addition of a solution of trifluoroborane diethyl etherate (1 M in toluene, 190 ml). The mixture is left stirring for 1.5 hours (TLC), solid sodium hydrogen carbonate is introduced and the mixture is filtered, washed with water, dried and concentrated. Chromatography on a column of silica (3/1 cyclohexane/ethyl acetate) gives 2 (37 g, 54%) [α]D−26 (c=1. dichloromethane). 1H NMR (CDCl3). δ 5.05-4.96 (m, 2H, H-2, H-4), 4.39, (d, 1H, J=9.5 Hz, H-1), 4.18-4.12 (m, 2H, H-6, H-6′), 3.60 (m, 1H, H-5), 3.50 (dd, 1H, J=9.3 Hz, H-3), 3.41 (s, 3H, OCH3), 2.65-2.53 (m, 2H, SCH2CH3), 2.12, 2.11, 2.09 (3s, 9H, 3 Ac), 1.25 (t, 1H, SCH2CH3)
Reaction SMILES: P(Cl)(Cl)(Cl)=O.[F:6][C:7]1[C:12]([F:13])=[C:11]([C:14]([NH2:16])=O)[C:10]([F:17])=[C:9]([F:18])[C:8]=1[CH3:19].Cl>C(Cl)Cl.N1C=CC=CC=1>[C:14]([C:11]1[C:10]([F:17])=[C:9]([F:18])[C:8]([CH3:19])=[C:7]([F:6])[C:12]=1[F:13])#[N:16]
Reactant: Cc1c(F)c(F)c(C(N)=O)c(F)c1F
Agent: Cl
Solvent: ClCCl
Solvent: O=P(Cl)(Cl)Cl
Solvent: c1ccncc1
Product: Cc1c(F)c(F)c(C#N)c(F)c1F
Temperature: 25 °C

Procedure:
A solution of phosphorus oxychloride (1.4 g) in methylene chloride (4 ml) was added slowly to a solution of 2,3,5,6-tetrafluoro-4-toluamide (1.0 g) in pyridine (8 ml) at -5° C. When the addition was complete the mixture was warmed to the ambient temperature over a period of 90 minutes, poured into a mixture of dilute hydrochloric acid and ice, and the resultant mixture was extracted with methylene chloride. After washing the extract with water (three times) and drying over anhydrous magnesium sulphate, the solvent was removed by evaporation under reduced pressure. The residual oil was purified by distillation under water pump pressure in a Kugelrohr apparatus to yield 4-cyano-2,3,5,6-tetrafluorotoluene, identified by infra red spectroscopy.
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][N:7]=[CH:6][CH:5]=1.C(N(CC)CC)C.[CH3:17][S:18](Cl)(=[O:20])=[O:19]>C1COCC1>[CH3:17][S:18]([O:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][N:7]=[CH:6][CH:5]=1)(=[O:20])=[O:19]
Reactant: OCCc1ccncc1
Reactant: CS(=O)(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCCc1ccncc1

Procedure:
The 4-(2-hydroxyethyl)pyridine (Lancaster, 0.153 g, 1.2 mmol), triethylamine (0.56 mL, 4.1 mmol), and methanesulfonyl chloride (0.15 mL, 1.9 mmol) in 10 mL THF were processed as described in Example 1C to give the title compound that was used directly in the next reaction.
Reaction SMILES: C([O:3][C:4](=[O:32])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH:19]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)C.[Li+].[OH-].Cl>C1COCC1.O>[CH2:25]([O:24][C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][CH:21]=1)[O:17][C:13]1[CH:14]=[C:15]([CH3:16])[C:7]2[CH:6]([CH2:5][C:4]([OH:32])=[O:3])[O:10][B:9]([OH:11])[C:8]=2[CH:12]=1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: CCOC(=O)CC1OB(O)c2cc(Oc3cccc(OCc4ccccc4)c3)cc(C)c21
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Cc1cc(Oc2cccc(OCc3ccccc3)c2)cc2c1C(CC(=O)O)OB2O
Temperature: 25 °C
Reaction time: 3 h
Yield: 91.4 %

Procedure:
To a solution of [6-(3-benzyloxy-phenoxy)-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid ethyl ester (1.0 g, 2.3 mmol) in THF (20 mL) at 0° C. was added a solution of LiOH (0.278 g, 11.5 mmol) in water (10 mL). The solution was allowed to warm to room temperature and stirred for 3 hours then acidified to pH 2 with 6M HCl. The solution was extracted with ethyl acetate (2×50 mL) and the organic extracts washed with water, brine, dried over sodium sulfate and concentrated in vacuo to give [6-(3-benzyloxy-phenoxy)-1-hydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl]-acetic acid as a clear oil (0.85 g, 91%) which was used without further purification. 1H NMR (400 MHz, DMSO): δ 9.13 (s, 1H), 7.42-7.25 (m, 6H), 7.08 (s, 1H), 6.96 (s, 1H), 6.79 (dd, J=8.4, 2.0 Hz, 1H), 6.64 (s, 1H), 6.51 (d, J=6.8 Hz, 1H), 5.48 (d, J=7.6 Hz, 1H), 5.07 (s, 2H), 3.10 (dd, J=15.6, 2.4 Hz, 1H), 2.26 (s, 3H), 2.13-2.07 (m, 1H).
Reaction SMILES: [C:1]1([P:7]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C-:8]2[CH:12]=[CH:11][C:10](CCCCC(C)(CCC3OCCCO3)C)=[C:9]2[P:28]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:47]([P:50]([CH:56]([CH3:58])[CH3:57])[C-:51]1[CH:55]=[CH:54][CH:53]=[CH:52]1)([CH3:49])[CH3:48].[Fe+2:59].Cl.C(=O)([O-])O.[Na+].[CH2:66]1[CH2:70][O:69][CH2:68][CH2:67]1>>[C:1]1([P:7]([C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[C-:8]2[CH:12]=[C:11]([C:67]([CH3:68])([CH2:66][CH:70]=[O:69])[CH3:47])[CH:10]=[C:9]2[P:28]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:56]([P:50]([CH:47]([CH3:49])[CH3:48])[C-:51]1[CH:55]=[CH:54][CH:53]=[CH:52]1)([CH3:58])[CH3:57].[Fe+2:59]
Reactant: C1CCOC1
Reactant: CC(C)(CCCCc1cc[c-](P(c2ccccc2)c2ccccc2)c1P(c1ccccc1)c1ccccc1)CCC1OCCCO1
Agent: [Fe+2]
Agent: CC(C)P([c-]1cccc1)C(C)C
Agent: Cl
Product: CC(C)(CC=O)c1cc(P(c2ccccc2)c2ccccc2)[c-](P(c2ccccc2)c2ccccc2)c1
Reaction time: 2 h
Yield: 67 %

Procedure:
A solution of 1,2-bis(diphenylphosphino)-1′-diisopropylphosphino-4-[4-(1,3-dioxan-2-yl)-2-methylbut-2-yl]butylferrocene (1 g, 1.2 mmol) dissolved in 100 ml of THF is admixed with 15 ml of 2 N hydrochloric acid solution. After 2 hours with stirring at reflux, the reaction mixture is neutralized with saturated aqueous sodium hydrogencarbonate solution and extracted with 2×50 ml of CH2Cl2. The organic phase is dried over MgSO4 and concentrated on a rotary evaporator. The crude product obtained is purified by chromatography on silica gel (eluent AcOEt/heptane 1:4) to give 630 mg (ρ=67%) of 1,2-bis(diphenylphosphino)-1′-diisopropylphosphino-4-(4-oxo-2-methylbut-2-yl)ferrocene in the form of a red powder.
Reaction SMILES: [Si:1]([O:8][CH:9]1[CH2:13][CH2:12][C:11]([CH2:14][PH:15](=[O:20])[O:16][CH:17]([CH3:19])[CH3:18])=[CH:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]>CO.[Pd]>[Si:1]([O:8][C@@H:9]1[CH2:13][CH2:12][C@H:11]([CH2:14][PH:15](=[O:20])[O:16][CH:17]([CH3:18])[CH3:19])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC(C)O[PH](=O)CC1=CC(O[Si](C)(C)C(C)(C)C)CC1
Agent: [Pd]
Solvent: CO
Product: CC(C)O[PH](=O)C[C@H]1CC[C@@H](O[Si](C)(C)C(C)(C)C)C1

Procedure:
A solution of isopropyl (3-t-butyldimethylsilyloxycyclopentenyl)methylphosphinate (4) (3.4 g, 10.7 mmol) in methanol (30 cm3) was hydrogenated over palladium on carbon (50 mg) at 40 psi for 3 h. The catalyst was removed by filtration through celite which was washed with methanol (3×30 cm3). The solvent was removed in vacuo to yield the desired product in quantitative yield (>90% cis isomer (5) by nmr spectroscopy). Which was used in the next step without further purification (3.4g, 99%) (data for cis isomer only is reported): 1H NMR (300 MHz, CDCl3) δ 0.076 (6H, s), 0.90 (9H, s), 1.32 (6H, d, J=6.1 Hz, OCHCH3), 1.44 (3H, d, J=13.2 Hz, PCH3), 1.63-1.81 (3H, m, C(5)—H, C(5)—H′ and C(1)—H), 1.82-1.99 (2H, m, C(2)—H and C(4)—H), 2.09-2.21 (2H, m, C(2)—H′ and C(4)—H′), 4.26 (1H, m, C(3)—R), 4.65 (1H, m, OCHCH3), 13C NMR (75.46 MHz, CDCl3) δ −4.96 (Si(CH3)2, br. s), 11.07 and 12.28 (PCH3, d, JPC=91.0 and 91.0 Hz), 17.89 (OSiC(CH3)3, s), 23.99 and 24.01 (C5, s), 24.20 (POC(CH3)3, br. d, J=4.0 Hz), 25.68 (OSiC(CH3)3, br. s) 35.78 and 35.81 (C(2), s), 35.91 and 36.11 (C(4), br. s,), 36.11 and 36.17 (C(1), d, JPC=99.6 and 100.7 Hz), 68.25 (POCHCH3, br. d, 2JPOC=6.6 Hz), 73.80 (C(3), d, 3JPC=11.5 Hz), 31 P NMR (121 MHz, CDCl3) δ 57.9, 58.1, MS (CI) m/z 321 (91%) (MH+), 187 (100), 145 (75), (ESI) 321.2012 (M+-C15H34O3PSi requires 321.2015).