Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: COC1C=C(N2CCC(C3C=CC=CC=3N)C2)C=CC=1.Cl.[N:22]1([CH2:29][CH2:30][O:31][C:32]2[CH:40]=[CH:39][C:35]([C:36](O)=O)=[CH:34][CH:33]=2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.N1(CCOC2C=C[C:54]([CH2:55][NH:56][C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][C:58]=3[CH:63]3[CH2:67][CH2:66][N:65]([C:68]4[CH:73]=[CH:72][CH:71]=[C:70]([O:74][CH3:75])[CH:69]=4)[CH2:64]3)=CC=2)CCCCCC1>>[N:22]1([CH2:29][CH2:30][O:31][C:32]2[CH:40]=[CH:39][C:35]([CH2:36][CH2:54][CH2:55][NH:56][C:57]3[CH:62]=[CH:61][CH:60]=[CH:59][C:58]=3[CH:63]3[CH2:67][CH2:66][N:65]([C:68]4[CH:73]=[CH:72][CH:71]=[C:70]([O:74][CH3:75])[CH:69]=4)[CH2:64]3)=[CH:34][CH:33]=2)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1
Reactant: O=C(O)c1ccc(OCCN2CCCCCC2)cc1
Reactant: COc1cccc(N2CCC(c3ccccc3NCc3ccc(OCCN4CCCCCC4)cc3)C2)c1
Agent: COc1cccc(N2CCC(c3ccccc3N)C2)c1
Agent: Cl
Product: COc1cccc(N2CCC(c3ccccc3NCCCc3ccc(OCCN4CCCCCC4)cc3)C2)c1

Procedure:
Synthesized from 2-[1-(3-methoxyphenyl)pyrrolidin-3-yl]phenylamine and 4-(2-azepan-1-ylethoxy)benzoic acid hydrochloride according to an analogous method to Example 152, synthetic [4-(2-azepan-1-ylethoxy)benzyl]{2-[1-(3-methoxyphenyl)pyrrolidin-3-yl]phenyl}amine (180 mg) was used according to an analogous synthetic method to Example 36 to provide [4-(2-azepan-1-ylethoxy)benzyl]ethyl {2-[1-(3-methoxyphenyl)pyrrolidin-3-yl]phenyl}amine (153 mg). The total amount of this compound was used according to an analogous synthetic method to Example 111 to provide the title compound (140 mg).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1)[NH2:5].[CH3:13][N:14](C)C=O>[C-]#N.[Zn+2].[C-]#N.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>[NH2:5][C:4]1[CH:3]=[C:2]([CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=1)[C:13]#[N:14]
Reactant: CN(C)C=O
Reactant: Nc1cc(Br)cc(C(F)(F)F)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Product: N#Cc1cc(N)cc(C(F)(F)F)c1
Temperature: 80 °C
Reaction time: 20 h

Procedure:
A solution of 3-bromo-5-(trifluoromethyl)aniline (3.24 g, 13.5 mmol) in N,N-dimethylformamide (50 mL) was degassed by bubbling argon through the solution for 30 minutes. To the reaction was added zinc cyanide (0.872 g, 7.42 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.624 g, 0.54 mmol). The reaction was heated to 80° C. and stirred for 20 hours. The solvent was removed from the reaction under vacuum and the residue purified by silica chromatography (Biotage SP4, eluting 15% EtOAc in iso-hexane (4 column volumes) then a gradient from 15-30% (over 6 column volumes)) to yield the title compound as a colourless oil (2.20 g).
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[OH:13])[C:6]([O:8][CH3:9])=[O:7])=[O:2].[CH:14]1([Mg]Br)[CH2:16][CH2:15]1>C1COCC1>[CH:14]1([CH:1]([OH:2])[C:3]2[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=2[OH:13])[C:6]([O:8][CH3:9])=[O:7])[CH2:16][CH2:15]1
Reactant: Br[Mg]C1CC1
Reactant: COC(=O)c1ccc(O)c(C=O)c1
Solvent: C1CCOC1
Product: COC(=O)c1ccc(O)c(C(O)C2CC2)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
In an ice-bath, methyl 3-formyl-4-hydroxybenzoate T20.1 (900 mg, 5 mmol) (commercially available from Aldrich) was dissolved in 5 mL THF. Then cyclopropylmagnesium bromide, 0.5 m in THF (22000 μL, 11 mmol) (commercially available from Aldrich) was added slowly. The reaction was raised to room temperature immediately and stirred at room temperature for 2 hours. After quenching with 1N HCl 11 mL, the reaction was extracted with EtOAc and dried. Silica gel chromatography afforded 950 mg of the product T20.2 (85%).
Reaction SMILES: O[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[H-].[Na+].C([O-])([O-])=O.[Cs+].[Cs+].BrC(C)(C)C([NH2:24])=O>O1CCOCC1.CN1C(=O)N(C)CCC1.CN1C(=O)CCC1>[NH2:24][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2
Reactant: Oc1cccc2cccnc12
Reactant: CC(C)(Br)C(N)=O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: [H-]
Solvent: CN1CCCN(C)C1=O
Solvent: C1COCCO1
Solvent: CN1CCCC1=O
Product: Nc1cccc2cccnc12
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 41.4 %

Procedure:
To a solution of 8-hydroxyquinoline (537 mg, 3.70 mmol) in dioxane (20 mL) was added NaH (Aldrich, dry, 300 mg, 12.2 mmol) and Cs2CO3 (4.00 g, 12.2 mmol). The resulting mixture was stirred at room temperature for about 30 minutes, then 2-bromo-2-methyl-propanamide (2.03 g, 12.2 mmol) was added and the resulting mixture was stirred at reflux for 16 h. After the reflux period, NMP (20 mL), DMPU (2 mL), and NaH (Aldrich, dry, 100 mg, 4.07 mmol) were added. The resulting mixture was stirred at 150° C. for 72 h. The reaction was cooled to room temp., and partitioned between water (50 mL) and EtOAc (100 mL). The aqueous layer was extracted with EtOAc (100 mL) and the combined organics washed with water (2×50 mL), dried (Na2SO4), and concentrated to about 3 g of material. The brown oil was chromatographed on silica (200 mL, 4 cm diam. column), eluting with 30:70:1 EtOAc/hexane/NEt3 to obtain 8-aminoquinoline as an off-white solid (220 mg, 1.53 mmol, 41.3% yield).: mp 65-67° C. (lit. 62.5-64° C., Dewar, M. J. S. et. al., Journal of the Chemical Society, 1956, 2556 and 62.5-64° C., Richardson, A. et. al., Journal of Organic Chemistry, 1960, 25, 1138); 1H NMR (300 MHz, CDCl3) δ8.76 (dd, 1 H, J=4.23, 1.75 Hz), 8.06 (dd, 1 H, J=8.20, 1.96), 7.37-7.30 (om's, 2 H), 7.15 (dd, 1 H, J=8.01, 1.30), 6.92 (dd, 1 H, J=7.51, 1.42), 4.98 (br s, 2 H, N--H2); MS (EI) 144; Analysis: Calculated C 74.98, H 5.59, N 19.43; Found C 74.88, H 5.67, N 19.26.
Reaction SMILES: [C:1]([O:5][C:6]1[N:18]=[C:17](I)[C:16]([Cl:20])=[C:15]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[C:7]=1[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])([CH3:4])([CH3:3])[CH3:2].[CH3:26][N:27]1[C:35]2[C:30](=[CH:31][C:32](B(O)O)=[CH:33][CH:34]=2)[CH:29]=[CH:28]1.C([O-])([O-])=O.[K+].[K+]>C(#N)C>[C:1]([O:5][C:6]1[N:18]=[C:17]([C:32]2[CH:31]=[C:30]3[C:35](=[CH:34][CH:33]=2)[N:27]([CH3:26])[CH:28]=[CH:29]3)[C:16]([Cl:20])=[C:15]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[C:7]=1[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)c1c(OC(C)(C)C)nc(I)c(Cl)c1OC(C)(C)C
Reactant: Cn1ccc2cc(B(O)O)ccc21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: Cn1ccc2cc(-c3nc(OC(C)(C)C)c(C(=O)OC(C)(C)C)c(OC(C)(C)C)c3Cl)ccc21
Temperature: 80 °C
Reaction time: 3 h
Yield: 105.7 %

Procedure:
A mixture of tert-butyl 2,4-di-tert-butoxy-5-chloro-6-iodonicotinate (103 mg, 0.2 mmol), 1-methyl-1H-indol-5-ylboronic acid (53 mg, 0.3 mmol), PdCl2dppf (16 mg, 0.02 mmol), aqueous K2CO3 (2.0 M×0.4 mL, 0.8 mmol) in acetonitrile (1.0 mL) was stirred at 80° C. for 3 h and then extracted with ethyl acetate. The organic layers were combined and dried over sodium sulfate, evaporated and purified by silica chromatography (0-5% ethyl acetate in hexanes) to give tert-butyl 2,4-di-tert-butoxy-5-chloro-6-(1-methyl-1H-indol-5-yl)nicotinate (103 mg, 100%).
Reaction SMILES: C1O[C:4]2([CH2:9][CH2:8][C:7]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[CH3:17])(O)[CH2:6][CH2:5]2)[O:3]C1.Cl.[H][H]>O1CCOCC1.[Pd]>[CH3:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[CH:7]1[CH2:8][CH2:9][C:4](=[O:3])[CH2:5][CH2:6]1
Reactant: [H][H]
Reactant: Cc1ccccc1C1(O)CCC2(CC1)OCCO2
Agent: [Pd]
Agent: Cl
Solvent: C1COCCO1
Product: Cc1ccccc1C1CCC(=O)CC1
Temperature: 25 °C
Reaction time: 48 h
Yield: 35 %

Procedure:
A solution of 4-(2-methylphenyl)-4-hydroxycyclohexanone ethylene ketal from the preceding step in 800 mL dioxane was treated with 16 mL concentrated hydrochloric acid and 30 grams 10% palladium-on-carbon under 35 p.s.i. hydrogen for 24 hours, then filtered through Celite to remove the catalyst. The filtrate was treated with 230 mL water and stirred at room temperature for 48 hours. The solution was evaporated, the pH adjusted to 8 with saturated aqueous sodium bicarbonate solution, and extracted with methylene chloride. The organic layer was dried over sodium sulfate and evaporated. The residue was chromatographed on silica gel using ethyl acetate/hexanes as eluent to afford 33.3 grams (35%) of an oil.
Reaction SMILES: [CH:1](NC(C)C)(C)C.C([Li])CCC.Cl[C:14]1[C:19]([N:20]2[C:29](=[O:30])[C:28]3[C:23](=[CH:24][CH:25]=[C:26]([F:31])[CH:27]=3)[N:22]=[C:21]2[CH3:32])=[CH:18][CH:17]=[CH:16][N:15]=1.[C:33]([C:35]1[CH:44]=[CH:43][CH:42]=[CH:41][C:36]=1[C:37]([O:39][CH3:40])=[O:38])#[N:34]>O1CCCC1>[C:33]([C:35]1[CH:44]=[CH:43][CH:42]=[CH:41][C:36]=1[C:37]([O:39][CH3:40])=[O:38])#[N:34].[F:31][C:26]1[CH:27]=[C:28]2[C:23](=[CH:24][CH:25]=1)[N:22]=[C:21]([CH:32]=[C:37]([C:36]1[CH:41]=[CH:42][CH:43]=[CH:44][C:35]=1[C:33]#[N:34])[OH:38])[N:20]([C:19]1[C:14]([CH3:1])=[N:15][CH:16]=[CH:17][CH:18]=1)[C:29]2=[O:30]
Reactant: Cc1nc2ccc(F)cc2c(=O)n1-c1cccnc1Cl
Reactant: CC(C)NC(C)C
Agent: COC(=O)c1ccccc1C#N
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Cc1ncccc1-n1c(C=C(O)c2ccccc2C#N)nc2ccc(F)cc2c1=O
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 17 %

Procedure:
Two identical reactions were run side by side. A solution of diisopropylamine (0.120 mL, 0.91 mmol) in tetrahydrofuran (5.4 mL) was chilled to -78° C. and butyllithium (0.26 mL, 0.65 mmol, 2.5 N in hexanes) was added dropwise. The solution was stirred 10 minutes and then a solution 3-(2-chloro-pyridin-3-yl)-6-fluoro-2-methyl-3H-quinazolin-4-one (0.204 g, 0.70 mmol) in tetrahydrofuran (5 mL) was added dropwise. The solution became intense red and was stirred 30 minutes. In a separate vessel a solution of methyl 2-cyanobenzoate (1.02 g, 6.33 mmol) in tetrahydrofuran (15 mL) was prepared and chilled to -78° C. The cold red anion solution was added to the cold methyl 2-cyanobenzoate solution via canula over 30 seconds. The resulting mixture was stirred 1 hour at -78° C. and then quenched with saturated aqueous bicarbonate and warmed to ambient temperature. The mixture was diluted with water and repeatedly extracted with ethyl acetate. The combined extracts were washed with water and brine, dried over magnesium sulfate and concentrated. The residues from the two side by side reactions were combined and flash chromatographed on silica gel (40×220 mm) with elution proceeding as follows: 10% ethyl acetate/hexane (250 mL), nil; 20% ethyl acetate/hexane (250 mL), nil; 30% ethyl acetate/hexane (50 mL), unweighed impurity; 40% ethyl acetate/hexane (250 mL), unweighed recovered 3-(2-chloro-pyridin-3-yl)-6-fluoro-2-methyl-3H-quinazolin-4-one; 50% ethyl acetate/hexane (250 mL), nil; 60% ethyl acetate/hexane (250 mL), desired product (tlc Rf =0.3 with 50% ethyl acetate/hexane on silica gel). The product containing fractions were combined and concentrated. The residue was triturated with ether and the light yellow solid which formed was collected and dried to yield 0.093 g (17%) of 2-{2-[6-fluoro-3-(2-methyl-pyridin-3-yl)-4-oxo-3,4-dihydro-quinazolin-2-yl]-1-hydroxy-vinyl}-benzonitrile which had: mp 217-218° C.; 1H NMR δ8.60 (dd, J=3, 5 Hz, 1 H), 7.85 (dd, J=3, 8 Hz, 1 H), 7.81 (dd, J=2, 8 Hz, 1 H), 7.67 (d, J=7 Hz, 1 H), 7.58-7.42 (m, 6 H), 4.98 (s, 1 H). Analysis calculated for C21H12ClFN4O2 : C, 63.09; H, 2.89; N, 13.38. Found: C, 62.90; H, 2.81; N, 13.01.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][C:13]=1[CH3:14])[C:7]([O:9][CH3:10])=[O:8])(=[NH:3])[NH2:2].Br[CH:16]1[C:21](=O)[CH2:20][CH2:19][O:18][CH2:17]1.C(=O)([O-])[O-].[K+].[K+]>CC#N>[CH3:14][C:13]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][C:4]=1[C:1]1[NH:2][C:16]2[CH2:17][O:18][CH2:19][CH2:20][C:21]=2[N:3]=1
Reactant: O=C1CCOCC1Br
Reactant: COC(=O)c1ccc(C)c(C(=N)N)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COC(=O)c1ccc(C)c(-c2nc3c([nH]2)COCC3)c1
Temperature: 80 °C
Reaction time: 8 h
Yield: 39 %

Procedure:
A mixture of methyl 3-carbamimidoyl-4-methylbenzoate (compound 1.9, 400 mg, 1.98 mmol, 1.00 equiv, 95%), 3-bromodihydro-2H-pyran-4(3H)-one (compound 1.10.1, 750 mg, 2.09 mmol, 1.00 equiv), and potassium carbonate (580 mg, 4.20 mmol, 2.00 equiv) in CH3CN (15 mL) was stirred overnight at 80° C. under nitrogen. After cooling to ambient temperature, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in 50 mL of ethyl acetate and washed with 2×10 mL of H2O. The organic phase was dried over (Na2SO4) and concentrated under reduced pressure. The residue was purified using silica gel column chromatography and purified using ethyl acetate/petroleum ether (1/3) to yield 0.21 g (37%) of the title compound as a white solid.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([NH:13][C:14](=[O:26])[C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)=[CH:17][CH:16]=2)[CH:7]=[CH:8][C:9]=1[N+:10]([O-])=O)([O-])=O.[N:27]1([C:32]2[CH:39]=[CH:38][C:35]([CH:36]=O)=[CH:34][CH:33]=2)[CH2:31][CH2:30][CH2:29][CH2:28]1>>[N:21]1([C:18]2[CH:19]=[CH:20][C:15]([C:14]([NH:13][C:6]3[CH:7]=[CH:8][C:9]4[NH:10][C:36]([C:35]5[CH:34]=[CH:33][C:32]([N:27]6[CH2:31][CH2:30][CH2:29][CH2:28]6)=[CH:39][CH:38]=5)=[N:1][C:4]=4[CH:5]=3)=[O:26])=[CH:16][CH:17]=2)[CH2:25][CH2:24][CH2:23][CH2:22]1
Reactant: O=C(Nc1ccc([N+](=O)[O-])c([N+](=O)[O-])c1)c1ccc(N2CCCC2)cc1
Reactant: O=Cc1ccc(N2CCCC2)cc1
Product: O=C(Nc1ccc2[nH]c(-c3ccc(N4CCCC4)cc3)nc2c1)c1ccc(N2CCCC2)cc1

Procedure:
Compound 225 was prepared according to the procedure similar to that described in Scheme III from N-(3,4-dinitrophenyl)-4-pyrrolidinylbenzamide and 4-pyrrolidinylbenzaldehyde. [M+H]+ calcd for C28H29N5O: 452.25; found: 451.95.
Reaction SMILES: [Cl:1][CH:2]([CH3:28])[CH:3]([NH:15][C:16]([CH:18]1[CH2:24][CH2:23][CH:22]([CH2:25][CH2:26][CH3:27])[CH2:21][CH2:20][NH:19]1)=[O:17])[CH:4]1[CH:9]([OH:10])[CH:8]([OH:11])[CH:7]([OH:12])[CH:6]([S:13][CH3:14])[O:5]1.[N+](C1C=CC([O:38][C:39](=O)[O:40][CH2:41][C:42]2[O:43][C:44](=[O:48])[O:45][C:46]=2[CH3:47])=CC=1)([O-])=O>CN(C=O)C>[CH3:47][C:46]1[O:45][C:44](=[O:48])[O:43][C:42]=1[CH2:41][O:40][C:39]([N:19]1[CH2:20][CH2:21][CH:22]([CH2:25][CH2:26][CH3:27])[CH2:23][CH2:24][CH:18]1[C:16](=[O:17])[NH:15][CH:3]([CH:4]1[CH:9]([OH:10])[CH:8]([OH:11])[CH:7]([OH:12])[CH:6]([S:13][CH3:14])[O:5]1)[CH:2]([Cl:1])[CH3:28])=[O:38]
Reactant: CCCC1CCNC(C(=O)NC(C(C)Cl)C2OC(SC)C(O)C(O)C2O)CC1
Reactant: Cc1oc(=O)oc1COC(=O)Oc1ccc([N+](=O)[O-])cc1
Solvent: CN(C)C=O
Product: CCCC1CCC(C(=O)NC(C(C)Cl)C2OC(SC)C(O)C(O)C2O)N(C(=O)OCc2oc(=O)oc2C)CC1
Reaction time: 16 h
Yield: 33.6 %

Procedure:
The title compound from example 47 (54 mg, 0.12 mmol) was dissolved in dry DMF (5 mL), then solid KHCO3 (25 mg, 0.25 mmol) and carbonic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester 4-nitro-phenyl ester (40 mg, 0.14 mmol prepared as described in F. Sakamoto, et. al, Chem. Pharm. Bull. 1984, 32 (6), 2241-2348) were added. The resulting mixture was stirred for 16 h, and the solvents were removed under reduced pressure, then the residue was purified by chromatography on silica with 5% MeOH/DCM to provide the title compound (24 mg, 33%) as a white solid.
Reaction SMILES: [CH3:1][C:2]([CH3:15])([CH2:12][CH:13]=[CH2:14])[CH:3]([OH:11])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.CCN(C(C)C)C(C)C.O>C(Cl)Cl.CS(C)=O>[CH3:1][C:2]([CH3:15])([CH2:12][CH:13]=[CH2:14])[C:3](=[O:11])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: C=CCC(C)(C)C(O)Cc1ccccc1
Solvent: ClCCl
Solvent: O
Solvent: CS(C)=O
Product: C=CCC(C)(C)C(=O)Cc1ccccc1
Reaction time: 0.17 h
Yield: 101 %

Procedure:
To a solution of the product of Step 1 (15 g) and 50 mL of i-Pr2NEt in 250 mL of CH2Cl2 cooled at 0° C. was added dropwise a solution of sulfur trioxide pyridine complex (23.8 g) in 100 mL of DMSO. After stirring for 10 min, the reaction mixture was treated with 200 mL H2O and extracted with 200 mL of 1:1 EtOAc/hexane. The extract was dried over MgSO4 and concentrated to give 15 g of the title compound as a yellow oil.
Reaction SMILES: C(O)(C(F)(F)F)C(F)(F)F.[O:11]=[C:12]1[O:18][C@H:17]([C@H:19]([CH2:21][OH:22])[OH:20])[C:15]([OH:16])=[C:13]1[OH:14].[O:23]1[CH:25]2[CH2:26][CH2:27][CH2:28][CH2:29][CH:24]12>C(#N)C>[OH:23][CH:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH:25]1[O:16][C:15]1[C@@H:17]([C@H:19]([CH2:21][OH:22])[OH:20])[O:18][C:12](=[O:11])[C:13]=1[OH:14]
Reactant: C1CCC2OC2C1
Reactant: O=C1O[C@H]([C@@H](O)CO)C(O)=C1O
Solvent: CC#N
Solvent: OC(C(F)(F)F)C(F)(F)F
Product: O=C1O[C@H]([C@@H](O)CO)C(OC2CCCCC2O)=C1O
Temperature: 70 °C
Reaction time: 36 h

Procedure:
Under an argon atmosphere, 4 ml of 1,1,1,3,3,3-hexafluoro isopropanol and 12 ml of acetonitrile were added to L-ascorbic acid (1.00 g), and further, 1,2-epoxycyclohexane (1.42 g) was added. The mixture was heated up to 70° C. and stirred for 36 hours, then, concentrated under reduced pressure, and 3.65 g of the resultant residue was subjected to silica gel column chromatography. Thereafter, it was eluted with chloroform/methanol/water(volume ratio:20/3/0.3) to obtain two elution fractions (first eluted fraction: 244 mg, later eluted fraction: 217 mg). Based on the measurement results of high resolution mass analysis, infrared absorption spectrum, 1H-NMR, 13C-NMR and specific optical rotation on the resultant elution fractions, it was confirmed that these are two 3-O-(2-hydroxycyclohexyl) ascorbic acids which are in mutual stereoisomerism and both of them are represented by the following structural formula.
Reaction SMILES: [CH2:1]([P:3]([O-:9])[O:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH3:2].N12CCCN=C1CCCCC2.Cl[CH2:22][CH:23]=[C:24]([CH3:26])[CH3:25]>C1C=CC([P]([Ni]([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.C1(C)C=CC=CC=1>[CH2:1]([P:3]([CH2:22][CH:23]=[C:24]([CH3:26])[CH3:25])(=[O:9])[O:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH3:2]
Reactant: CC(C)=CCCl
Reactant: CCCCOP([O-])CC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Ni]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: C1CCC2=NCCCN2CC1
Product: CCCCOP(=O)(CC)CC=C(C)C
Yield: 75.8 %

Procedure:
At room temperature, a three-neck flask equipped with stirrer and high-performance condenser is initially charged with 400 g of toluene and this initial charge is devolatilized by stirring and passing nitrogen through it. Then, under nitrogen, 6.65 g (6 mmol) of tetrakis(triphenylphosphine)nickel and 30 g (0.2 mol) of butyl ethylphosphonite (produced as in Example 2) and 30.4 g (0.2 mol) of 1,8-diazabicyclo[5.4.0]undec-7-ene are added followed by the dropwise addition of 20.9 g (0.2 mol) of 1-chloro-3-methyl-2-butene. Following a reaction time of 5 hours, the reaction solution is passed for purification through a column charged with Deloxan® THP Hand the solvent is removed in vacuo. The product is purified by column chromatography to obtain 33.1 g (76% of theory) of butyl ethyl(3-methyl-2-butenyl)phosphinate as colorless oil.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[S:9][CH:10]=[C:11]([CH2:13][O:14][CH2:15][CH2:16][O:17][CH3:18])[N:12]=1)(C)(C)C.[ClH:20].O1CCOCC1>>[ClH:20].[CH3:18][O:17][CH2:16][CH2:15][O:14][CH2:13][C:11]1[N:12]=[C:8]([NH2:7])[S:9][CH:10]=1
Reactant: COCCOCc1csc(NC(=O)OC(C)(C)C)n1
Agent: Cl
Solvent: C1COCCO1
Product: COCCOCc1csc(N)n1

Procedure:
Carbamate III (Example 4) (225 mg, 781 μmol) was stirred at ambient temperature with HCl/dioxane (4 M, 4 ml) for 18 hours. Volatiles were removed under reduced pressure and the residue was azeotroped several times with toluene. 1H NMR (300 MHz, CD3OD) δ 3.37 (s, 1H), 3.55-3.59 (m, 2H), 3.64-3.68 (m, 2H), 4.43 (s, 2H), 6.82 (s, 1H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[Mg].[B:19](OC)([O:22]C)[O:20]C>BrCCBr.C1COCC1>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([B:19]([OH:22])[OH:20])=[C:3]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:4]=1
Reactant: COB(OC)OC
Reactant: COc1ccc(Br)c(OCc2ccccc2)c1
Agent: [Mg]
Solvent: BrCCBr
Solvent: C1CCOC1
Product: COc1ccc(B(O)O)c(OCc2ccccc2)c1
Temperature: -78 °C
Reaction time: 1.5 h
Yield: 84.3 %

Procedure:
A 2 L three-necked flask equipped with thermometer, reflux condenser and mechanical stirrer was charged with 1-bromo-4-methoxy-2-(phenylmethoxy)benzene (43.0 g, 0.147 mol), anhydrous THF (600 mL) under nitrogen. Magnesium turnings (4.2 g, 0.17 mol) and 1,2-dibromoethane (0.5 mL, 6 mmol) was then added and the mixture heated to reflux. After 1.5 h, the reaction was cooled to -78° C. and B(OMe)3 (33.4 mL, 0.294 mol) added dropwise while maintaining an internal temperature below -60° C. Upon complete addition, the reaction was quenched with 5% HCl (15 mL) to pH=3.0, portioned with EtOAc (100 mL), the organic phase separated, washed with brine (100 mL), dried (MgSO4) and concentrated in vacuo giving a pale yellow solid. The solid was triturated with hexane (90 mL), filtered and dried to afford [4-methoxy-2(phenylmethoxy)phenyl] boronic acid as a pale white solid (32 g, 85%): mp 127.0-129.0° C.; 1H NMR δ 7.8 (d, J=8.2 Hz, 1 H), 7.5-7.3 (m, 5 H), 6.6 (dd, J=8.2, 2.7 Hz, 1 H), 6.55 (d, J=2.7 Hz, 1 H), 5.65 (s, 2 H), 5.15 (s, 2 H), 3.85 (s, 3 H).
Reaction SMILES: Cl.[C:2]1([C:8]2([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:16]3[CH:12]([CH2:13][NH:14][CH2:15]3)[C:11]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[O:24][CH3:25])([OH:17])[CH:10]([OH:26])[CH2:9]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:40][O:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=1[CH2:48][C:49](O)=[O:50]>ClCCl>[C:27]1([C:8]2([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:16]3[CH:12]([CH2:13][NH:14][CH:15]3[C:49](=[O:50])[CH2:48][C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=3[O:41][CH3:40])[C:11]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[O:24][CH3:25])([OH:17])[CH:10]([OH:26])[CH2:9]2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: COc1ccccc1CC(=O)O
Reactant: COc1ccccc1C1(O)C(O)CC(c2ccccc2)(c2ccccc2)C2CNCC21
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccccc1CC(=O)C1NCC2C1C(c1ccccc1)(c1ccccc1)CC(O)C2(O)c1ccccc1OC
Reaction time: 1.5 h
Yield: 77.5 %

Procedure:
To a solution of 4.5 g of (3aRS,4RS,5RS,7aRS)-7,7-diphenyl-4-(2-methoxyphenyl)perhydro-4,5-isoindolediol hydrochloride in 100 cm3 of dichloromethane, cooled to 0° C., are added 4.2 cm3 of triethylamine, followed by 2.4 g of (2-methoxyphenyl)acetic acid in 50 cm3 of dichloromethane. Stirring is carried out at room temperature for 90 minutes; the reaction mixture is washed with twice 10 cm3 of water, dried over magnesium sulphate and concentrated to dryness under reduced pressure (2.7 kPa). The crystallized solid is taken up with 100 cm3 of diisopropyl ether and then filtered, washed with 50 cm3 of saturated sodium bicarbonate solution and then with 50 cm3 of diisopropyl ether. 4.35 g of (3aRS,4RS,5RS,7aRS)-7,7-diphenyl-4-(2-methoxyphenyl)-2-(2-methoxyphenyl)acetylperhydro-4,5-isoindolediol are obtained, in the form of a light beige solid melting at 278° C.
Reaction SMILES: [CH3:1][Li].[SiH3][SiH3].[CH3:5][Si:6]([CH3:18])([O:15][CH2:16][CH3:17])[Si:7]([CH3:14])([O:11][CH2:12][CH3:13])OCC>>[CH3:18][Si:6]([CH3:5])([O:15][CH2:16][CH3:17])[Si:7]([CH3:1])([CH3:14])[O:11][CH2:12][CH3:13]
Reactant: [Li]C
Reactant: CCO[Si](C)(C)[Si](C)(OCC)OCC
Agent: [SiH3][SiH3]
Product: CCO[Si](C)(C)[Si](C)(C)OCC

Procedure:
In the same manner as in Example 1, change of the average molecular weight of the resulting polysilanes was examined by changing the amount of methyl lithium to be used as a reaction starting compound. The results including those of Example 1 and the yields and properties of the products are shown in Table 1. In Example 4, after the disilane compound and methyl lithium were reacted, the reaction mixture was applied to gas chromatography before heating to confirm that 1,1,2-trimethyl-1,2,2-triethoxydisilane and 1,1,2,2-tetramethyl-1,2-diethoxydisilane were produced. From the reaction mixture of Example 4, no solid was obtained by reprecipitation so that low boiling point compounds were removed under conditions of 180° C. and 1 Torr to give a final product.