Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[CH3:11][O:12][C:13](=[O:21])[CH2:14][CH:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1.[CH3:22]I>O1CCCC1.O>[CH:15]1([CH:14]([CH3:22])[C:13]([O:12][CH3:11])=[O:21])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]1
Reactant: COC(=O)CC1CCCCC1
Reactant: CI
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: COC(=O)C(C)C1CCCCC1
Temperature: -78 °C
Reaction time: 1 h
Yield: 92.7 %

Procedure:
1.0 M of Lithium hexamethyldisilazide in tetrahydrofuran (2.2 mL, 2.2 mmol) was added to a solution of methylcyclohexylacetate (0.30 g, 1.9 mmol) (Aldrich, Cat. #209600) in tetrahydrofuran (7.0 mL) at −78° C. The mixture was stirred at −78° C. for 1 h., then methyl iodide (0.14 mL, 2.3 mmol) was added. The mixture was allowed to warm slowly to r.t., and stirred at r.t. overnight. The mixture was diluted with water, and extracted with ethyl acetate (3×10 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-10%) to afford the desired product (0.30 g, 92%).
Reaction SMILES: [C:1]1([C:7]2C=CC=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([Zn]CC)C.C(=[O:25])C1C=CC=CC=1>C1(C)C=CC=CC=1>[C:1]1([C@H:7]([OH:25])[CH2:8][CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: c1ccc(-c2ccccc2)cc1
Reactant: O=Cc1ccccc1
Agent: CC[Zn]CC
Solvent: Cc1ccccc1
Product: CC[C@@H](O)c1ccccc1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 89 %

Procedure:
To a Schlenk flask containing toluene (10 mL) (dried with Na and degassed with N2) was added the polymer of Example 1(28 mg, 0.05 mmol based on the biphenyl subunit) and diethylzinc (0.14 mL, 1.3 mmol) under N2 at room temperature. After ca. 15 min, the flask was cooled to 0° C. and benzaldehyde (0.1 mL, 1 mmol) was added in a dropwise manner. Stirring was continued at this temperature for 10 h. The 1H NMR spectrum of the crude mixture showed 100% conversion with no side product. The reaction was then quenched with the addition of 1N HCl at 0° C. and the aqueous layer was extracted with diethyl ether. The combined organic layer was washed with brine until pH 7 and then dried over anhydrous Na2SO4. Concentration in vacuum gave a pale yellow oil, which upon treatment with MeOH (20 mL) precipitated the polymer. The filtrate was concentrated and purified by column chromatography on silica gel (eluent: EtOAc/hexanes 1/4) to afford (R)-1-phenyl-1propanol as a colorless liquid (122 mg, 89%). 1H NMR (270 MHz, CDCl3) δ0.91 (t, J=7.4, 3H), 1.78 (dq, J=7.3, 6.4, 2H), 1.89 (br, 1H), 4.58 (t, J=6.5, 1H), 7.25-7.37 (m, 5H) . [α]D =42.91 (c=2.44, CHCl3). The ee value was determined to be 92% on GC with a chiral column (α-Dex capillary column, Supelco Company). The recycled catalyst showed the similar reactivity and the same ee for the product.
Reaction SMILES: Cl.[CH2:2]([N:6]1[C@@H:10]([C:11](OC)=O)[CH2:9][S:8][C:7]1=[N:15][C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][C:17]=1[CH3:25])[CH:3]([CH3:5])[CH3:4].C(N1C(=C)C(=O)SC1=N[C:38]1[CH:43]=CC([N+]([O-])=O)=[CH:40][C:39]=1[CH3:47])C(C)C>CCOC(C)=O>[CH3:25][C:17]1[CH:18]=[C:19]([N+:22]([O-:24])=[O:23])[CH:20]=[CH:21][C:16]=1[N:15]=[C:7]1[N:6]([CH2:2][CH:3]([CH3:5])[CH3:4])[C:10]2([CH2:40][CH:39]3[CH2:47][CH:11]2[CH2:43][CH2:38]3)[CH2:9][S:8]1
Reactant: COC(=O)[C@H]1CSC(=Nc2ccc([N+](=O)[O-])cc2C)N1CC(C)C
Reactant: C=C1C(=O)SC(=Nc2ccc([N+](=O)[O-])cc2C)N1CC(C)C
Agent: Cl
Solvent: CCOC(C)=O
Product: Cc1cc([N+](=O)[O-])ccc1N=C1SCC2(CC3CCC2C3)N1CC(C)C

Procedure:
(R)-N-Isobutylserine methyl ester HCl salt (Method B3a; 2.28 g, 10.8 mmol) was treated with SOCl2 followed by 2-methyl-4-nitrophenyl isothiocyanate in a manner analogous to Method C2a. The resulting material was purified by column chromatography (SiO2, gradient from hexane to 10% EtOAc/hex) to give 3-isobutyl-4-methylene-2-(2-methyl-4-nitrophenylimino)-1,3-thiazolidin-5-one (0.028 g, 10%) followed by (S)-3-isobutyl-4-carbomethoxy-2-(2-methyl-4-nitrophenylimino)-1,3-thiazolidine HCl salt (0.192 g, 56%). 3-Isobutyl-4-methylene-2-(2-methyl-4-nitrophenylimino)-1,3-thiazolidin-5-one: TLC (25% EtOAc/hex) Rf 0.40. (S)-3-isobutyl-4-carbomethoxy-2-(2-methyl-4-nitrophenylimino)-1,3-thiazolidine HCl salt: TLC (free base, 25% EtOAc/hex) Rf0.50.
Reaction SMILES: [F:1][C:2]([F:26])([F:25])[O:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][NH:14][CH2:13][CH:12]([NH:16][C:17](=[O:24])[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:11]2)=[CH:6][CH:5]=1.C(N(CC)CC)C.[C:34](Cl)(=[O:45])[O:35][C:36]1[CH:41]=[CH:40][C:39]([N+:42]([O-:44])=[O:43])=[CH:38][CH:37]=1.C(=O)(O)[O-].[Na+]>ClCCl.O>[C:18]1([C:17]([NH:16][CH:12]2[CH2:11][CH:10]([C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:25])[F:26])=[CH:9][CH:8]=3)[CH2:15][N:14]([C:34]([O:35][C:36]3[CH:37]=[CH:38][C:39]([N+:42]([O-:44])=[O:43])=[CH:40][CH:41]=3)=[O:45])[CH2:13]2)=[O:24])[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Reactant: O=C(NC1CNCC(c2ccc(OC(F)(F)F)cc2)C1)c1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: O=C(NC1CC(c2ccc(OC(F)(F)F)cc2)CN(C(=O)Oc2ccc([N+](=O)[O-])cc2)C1)c1ccccc1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
At 0° C., 200 mg (0.55 mmol) of N-{5-[4-(trifluoromethoxy)phenyl]piperidin-3-yl}benzamide and 153 μl (1 l mmol) of triethylamine were initially charged in 17 ml of dichloromethane, and 111 mg (0.55 mmol) of 4-nitrophenyl chlorocarbonate were added slowly. The mixture was stirred at 0° C. for 2 h and then warmed to RT. Water and saturated aqueous sodium bicarbonate solution were added, and the reaction mixture was extracted. The organic phase was dried over sodium sulphate and concentrated under reduced pressure. The crude product was then purified by preparative HPLC (Reprosil C18, water/acetonitrile gradient). Yield: 254 mg (87% of theory)
Reaction SMILES: [CH2:1]([SiH:5]([CH2:10][CH2:11][CH2:12][CH3:13])[CH2:6][CH2:7][CH2:8][CH3:9])[CH2:2][CH2:3][CH3:4].Cl[SiH](Cl)Cl.C([Mg]Cl)CCC.[H][H].[CH3:26][OH:27]>[Pd].O>[CH2:10]([Si:5]([CH2:1][CH2:2][CH2:3][CH3:4])([CH2:6][CH2:7][CH2:8][CH3:9])[O:27][CH3:26])[CH2:11][CH2:12][CH3:13]
Reactant: [H][H]
Reactant: CCCC[SiH](CCCC)CCCC
Reactant: CO
Agent: [Pd]
Agent: CCCC[Mg]Cl
Agent: Cl[SiH](Cl)Cl
Solvent: O
Product: CCCC[Si](CCCC)(CCCC)OC

Procedure:
In a 500 ml four-neck flask provided with reflux condenser, precision glass stirrer and thermometer, 1.2 g of 5% palladium on activated carbon, water-free (commercially available from Sigma-Aldrich Corp., USA) were suspended in 23.7 g of methanol. 124 g of tri-n-butylsilane (prepared from trichlorosilane and n-butylmagnesium chloride by a method customary in organic chemistry) were subsequently introduced at room temperature over a period of one hour while stirring. After addition of the first drops of the SiH-functional siloxane, spontaneous hydrogen evolution commenced. The temperature of the reaction mixture rose to a maximum of 35° C. After the addition was complete, the mixture was allowed to react further until gas evolution could no longer be observed at the attached bubble counter, the black precipitate was filtered on a pressure filter and the colorless clear filtrate was distilled via a 20 cm Vigreux column. After the first fraction, which according to gas-chromatographic analysis consisted mainly of methanol, 134 g of tributylmethoxysilane having a GC purity of 99.5% by area distilled over at a boiling temperature of 112° C. at 10 hPa.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH3:10])=[C:7]([CH:9]=1)[NH2:8].C(N(CC)CC)C.[Cl:18][CH2:19][C:20](Cl)=[O:21].Cl>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH3:10])=[C:7]([NH:8][C:20](=[O:21])[CH2:19][Cl:18])[CH:9]=1
Reactant: O=C(Cl)CCl
Reactant: COc1ccc(C)c(N)c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc(C)c(NC(=O)CCl)c1
Reaction time: 0.75 h

Procedure:
To a solution of 5-methoxy-2-methylaniline (7.62 g) and triethylamine (15.5 ml) in dichloromethane (150 ml) at 0-5° C. was added chloroacetyl chloride (5.0 ml) dropwise and the ice bath removed. The resulting reaction mixture was stirred for 45 min before being poured into dil HCl and extracted with dichloromethane. Organic extracts were combined, washed with water, dried (Na2SO4) and concentrated to give a brown solid that was triturated with diethyl ether to leave the sub-title compound as a beige solid (5.7 g).
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[NH2:6][C:7]1[CH:37]=[CH:36][C:10]([CH2:11][N:12]2[C:16](=[O:17])[C:15]3([CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]3)[N:14]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[CH2:13]2)=[CH:9][CH:8]=1.N1C=CC=CC=1>ClCCl>[CH3:1][S:2]([NH:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:11][N:12]2[C:16](=[O:17])[C:15]3([CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]3)[N:14]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[CH2:13]2)=[CH:36][CH:37]=1)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)N1CCC2(CC1)C(=O)N(Cc1ccc(N)cc1)CN2c1ccccc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC2(CC1)C(=O)N(Cc1ccc(NS(C)(=O)=O)cc1)CN2c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 92.1 %

Procedure:
Methanesulfonyl chloride (0.39 mL, 5.02 mmol) was added dropwise at 0° C. to tert-butyl 3-(4-aminobenzyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decane-8-carboxylate (2.19 g, 5.02 mmol) and pyridine (0.61 mL, 7.53 mmol) in dichloromethane (10 mL). The reaction was allowed to warm to room temperature and stirred for 30 minutes. The mixture was diluted with dichloromethane, washed with 2M aqueous hydrochloric acid and brine, dried (MgSO4) and evaporated. The residue was purified by PTLC (50% ethyl acetate/hexanes) to give product as an oil (2.38 g, 92%); 1H NMR (DMSO-d6); δ1.45 (s, 9H); 1.63 (d, J=14 Hz, 2H); 2.18-2.23 (m, 2H); 2.98 (s, 3H); 3.30-3.55 (m, 2H); 3.80-3.95 (m, 2H); 4.52 (s, 2H); 4.59 (s, 2H); 6.67 (d, J=8 Hz, 2H); 6.76 (t, J=7.2 Hz, 2H); 7.15-7.21 (m, 4H); 7.26-7.28 (m, 2H); MS for C26H34N4O5S m/z 515 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[NH:14][CH2:15][C:16]2[N:17]([CH3:21])[CH:18]=[CH:19][N:20]=2)=[C:4]([O:22][CH3:23])[CH:3]=1.[CH3:24][S:25]([C:28]1[CH:29]=[C:30]([CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:36]=1)[C:31](O)=[O:32])(=[O:27])=[O:26]>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH2:15][C:16]2[N:17]([CH3:21])[CH:18]=[CH:19][N:20]=2)[C:31](=[O:32])[C:30]2[CH:34]=[C:35]([C:37]([F:40])([F:38])[F:39])[CH:36]=[C:28]([S:25]([CH3:24])(=[O:27])=[O:26])[CH:29]=2)=[C:4]([O:22][CH3:23])[CH:3]=1
Reactant: COc1cc(F)ccc1-c1ccncc1NCc1nccn1C
Reactant: CS(=O)(=O)c1cc(C(=O)O)cc(C(F)(F)F)c1
Product: COc1cc(F)ccc1-c1ccncc1N(Cc1nccn1C)C(=O)c1cc(C(F)(F)F)cc(S(C)(=O)=O)c1

Procedure:
The title compound was prepared in analogy to example 90, from [4-(4-fluoro-2-methoxy-phenyl)-pyridin-3-yl]-(1-methyl-1H-imidazol-2-ylmethyl)-amine and 3-(methylsulfonyl)-5-(trifluoromethyl)benzoic acid (example 114, intermediate a) after a reaction time of 18 hours at room temperature. The compound was purified by silica gel chromatography on a 20 g column using an MPLC (Flashmaster) system eluting with a gradient of CH2Cl2:MeOH (100:0 to 80:15). Further purification by preparative HPLC (Gemini NX) with a gradient of MeOH:water (containing 0.05% formic acid) (80:20 to 98:2). Light yellow foam (54%). MS (ESI): m/z=563.135 [M+H]+.
Reaction SMILES: [C:1]1([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:6]=[C:5]([CH:7]=O)[CH:4]=[C:3]([CH:9]=O)[CH:2]=1.[NH2:17][CH2:18][CH2:19][CH2:20][NH:21][CH2:22][CH2:23][CH2:24][NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29].[BH4-].[Na+].[OH-:35].[Na+]>CCOC(C)=O.CO>[C:1]1([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH:6]=[C:5]([CH2:7][NH:17][CH2:18][CH2:19][CH2:20][NH:21][CH2:22][CH2:23][CH2:24][NH:25][C:26](=[O:32])[O:27][C:28]([CH3:29])([CH3:31])[CH3:30])[CH:4]=[C:3]([CH2:9][NH:17][CH2:18][CH2:19][CH2:20][NH:21][CH2:22][CH2:23][CH2:24][NH:25][C:26](=[O:27])[O:35][C:28]([CH3:30])([CH3:29])[CH3:31])[CH:2]=1
Reactant: O=Cc1cc(C=O)cc(-c2ccccc2)c1
Reactant: CC(C)(C)OC(=O)NCCCNCCCN
Reactant: [OH-]
Agent: [BH4-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CO
Product: CC(C)(C)OC(=O)NCCCNCCCNCc1cc(CNCCCNCCCNC(=O)OC(C)(C)C)cc(-c2ccccc2)c1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
[1,1′-Biphenyl]-3,5-dicarbaldehyde (3.62 g, 17.2 mmol, 1) and MeOH (100 mL) were added to a round-bottom flask. To the solution was added tert-butyl (3-((3-aminopropyl)amino)propyl)-carbamate (7.96 g, 34.4 mmol), and the reaction mixture was stirred at rt for 24 h. Sodium borohydride (2.62 g, 69.0 mmol) was added and the reaction mixture stirred for 1 h. The reaction mixture was concentrated under reduced pressure to afford a white solid. Aqueous NaOH (10%, 200 mL) and EtOAc (200 mL) were added, and the reaction mixture was stirred for 1 h. The layers were separated, and the aqueous layer was extracted with EtOAc (200 mL). The organic layers were combined, dried over Na2SO4, filtered, and concentrated under reduced pressure to afford a clear oil that was used without further purification.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C@H:12]([CH2:16][C:17]#[CH:18])[C:13]([OH:15])=[O:14])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[N:19]([C@@H:22]1[CH2:31][CH2:30][CH2:29][C:28]2[CH:27]=[C:26]([C:32]([O:34][CH3:35])=[O:33])[CH:25]=[CH:24][C:23]1=2)=[N+:20]=[N-:21].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>CC(O)(C)C.O>[CH3:35][O:34][C:32]([C:26]1[CH:27]=[C:28]2[C:23](=[CH:24][CH:25]=1)[C@H:22]([N:19]1[CH:18]=[C:17]([CH2:16][C@@H:12]([NH:11][S:8]([C:5]3[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=3)(=[O:9])=[O:10])[C:13]([OH:15])=[O:14])[N:21]=[N:20]1)[CH2:31][CH2:30][CH2:29]2)=[O:33]
Reactant: C#CC[C@@H](NS(=O)(=O)c1ccc(C)cc1)C(=O)O
Reactant: COC(=O)c1ccc2c(c1)CCC[C@H]2N=[N+]=[N-]
Agent: O=C1O[C@H]([C@@H](O)CO)C([O-])=C1O
Agent: [Na+]
Solvent: O
Solvent: CC(C)(C)O
Product: COC(=O)c1ccc2c(c1)CCC[C@H]2n1cc(C[C@@H](NS(=O)(=O)c2ccc(C)cc2)C(=O)O)nn1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A solution of (R)-2-(4-methylbenzenesulfonamido)pent-4-ynoic acid (6.25 g, 23.4 mmol) and (R)-methyl 5-azido-5,6,7,8-tetrahydronaphthalene-2-carboxylate (5.4 g, 23.4 mmol) in 80 mL t-BuOH was treated with sodium ascorbate (0.47 g, 2.34 mmole in 24 mL H2O) and CuSO4.5H2O (0.58 g, 2.34 mmol in 24 mL H2O). An additional portion of H2O (50 mL) was then added to the reaction mixture. After stirring for 48 h at RT, the reaction mixture was diluted with H2O. A precipitate had formed that was filtered and air-dried. MS (m/z): 499.4 (m+H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[C:11]([N+:13]([O-])=O)[CH:12]=1)[N:9]=[CH:8][CH:7]=[CH:6]2.C(O)(=O)C.[OH-].[Na+]>CO.O=[Pt]=O>[NH2:13][C:11]1[CH:12]=[C:3]([O:2][CH3:1])[CH:4]=[C:5]2[C:10]=1[NH:9][CH2:8][CH2:7][CH2:6]2
Reactant: COc1cc([N+](=O)[O-])c2ncccc2c1
Agent: O=[Pt]=O
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: CC(=O)O
Product: COc1cc(N)c2c(c1)CCCN2
Reaction time: 2.5 h

Procedure:
A suspension of 6-methoxy-8-nitroquinoline (20 g, 98 mmol) in methanol (200 ml) was hydrogenated over PtO2 (0.5 g) at 50 p.s.i. for 2.5 hours. The solution was treated with acetic acid (11.5 ml, 200 mmol) and PtO2 (0.5 g) and hydrogenated at 50 p.s.i. for 18 hours. The catalyst was removed by filtration and the solution evaporated in vacuo to give an oil. The residue was basified with 1 N-sodium hydroxide (200 ml) and the aqueous mixture extracted with diethyl ether (2×200 ml). The extracts were dried (MgSO4) and evaporated in vacuo to give crude 8-amino-1,2,3,4-tetrahydro-6-methoxyquinoline as a red oil.
Reaction SMILES: [CH3:1][C:2]1[O:3][CH:4]=[CH:5][C:6]=1[CH3:7].C([Li])CCC.[C:13]([C:15]1[N:20]=[CH:19][CH:18]=[CH:17][N:16]=1)#N.Cl.C([O:24]CC)C>CCCCCC>[CH3:7][C:6]1[CH:5]=[C:4]([C:13]([C:15]2[N:20]=[CH:19][CH:18]=[CH:17][N:16]=2)=[O:24])[O:3][C:2]=1[CH3:1]
Reactant: N#Cc1ncccn1
Reactant: Cc1ccoc1C
Reactant: CCOCC
Agent: Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Product: Cc1cc(C(=O)c2ncccn2)oc1C
Temperature: -78 °C
Yield: 7 %

Procedure:
2,3-Dimethylfuran (1.5 g) was dissolved in diethyl ether (20 ml) under an argon atmosphere to prepare a solution. A 1.6 M hexane solution (10.9 ml) of n-butyllithium was added dropwise to the solution at 0° C., and the mixture was stirred under reflux for 2.5 hr. Thereafter, the reaction solution was cooled to −78° C., a solution of 2-cyanopyrimidine (1.8 g) in diethyl ether (8 ml) was added dropwise thereto, and the mixture was stirred at room temperature overnight. The reaction solution was poured into ice to stop the reaction. The mixture was acidified with 1 M hydrochloric acid and was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by column chromatography using chloroform-acetone to give (4,5-dimethylfuran-2-yl)-(2-pyrimidyl)-methanone (226 mg, yield 7%).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:24]=[CH:23][CH:22]=[CH:21][C:6]=1[O:7][CH2:8][CH2:9][C:10]1[CH:20]=[CH:19][C:13]([O:14][CH2:15][C:16]([OH:18])=O)=[CH:12][CH:11]=1)=[O:4].[F:25][C:26]1[CH:35]=[CH:34][CH:33]=[CH:32][C:27]=1[CH2:28][NH:29][CH2:30][CH3:31].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[CH2:30]([N:29]([CH2:28][C:27]1[CH:32]=[CH:33][CH:34]=[CH:35][C:26]=1[F:25])[C:16](=[O:18])[CH2:15][O:14][C:13]1[CH:12]=[CH:11][C:10]([CH2:9][CH2:8][O:7][C:6]2[CH:21]=[CH:22][CH:23]=[CH:24][C:5]=2[C:3]([O:2][CH3:1])=[O:4])=[CH:20][CH:19]=1)[CH3:31]
Reactant: CCNCc1ccccc1F
Reactant: COC(=O)c1ccccc1OCCc1ccc(OCC(=O)O)cc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCN(Cc1ccccc1F)C(=O)COc1ccc(CCOc2ccccc2C(=O)OC)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 51.5 %

Procedure:
(4-{2-[2-(Methoxycarbonyl)phenoxy]ethyl}phenoxy)acetic acid (0.200 mg, 0.605 mmol) was dissolved in DMF and cooled on an ice-bath N-(2-Fluorobenzyl) ethanamine (0.102 g, 0.666 mmol), TBTU (0.214 g, 0.666 mmol) and DIPEA (0.22 ml, 1.271 mmol) was added. The reaction mixture was stirred for 16 h at room temperature. EtOAc was added and the organic phase was washed with two portions of 20 ml NaCO3 (sat). The organic layer was dried with MgSO4 and the solvent was removed by evaporation. The crude was purified by preparative HPLC (starting with acetonitrile/buffer 60/40 and then increasing the acetonitrile concentration to 100% acetonitrile in 25 min, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M), column KR-100-7-C8, 50*500, flow 80 ml/min). 145 mg of the desired product was obtained after freeze drying (yield 71.1%).
Reaction SMILES: [CH2:1]([O:3][CH:4]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:2]>P([O-])([O-])([O-])=O>[CH2:1]([O:3][C@@H:4]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=1)[C:5]([OH:7])=[O:6])[CH3:2].[CH2:1]([O:3][C@H:4]([CH2:10][C:11]1[CH:12]=[CH:13][C:14]([OH:17])=[CH:15][CH:16]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:2]
Reactant: CCOC(=O)C(Cc1ccc(O)cc1)OCC
Agent: O=P([O-])([O-])[O-]
Product: CCOC(=O)[C@@H](Cc1ccc(O)cc1)OCC
Product: CCO[C@@H](Cc1ccc(O)cc1)C(=O)O
Temperature: 25 °C

Procedure:
To ethyl (2RS) (+/−) 2-ethoxy-3-(4-hydroxyphenyl)-propanoate (0.25 ml of a solution containing 2 mg/ml in phosphate 0.1M buffer pH 7) was added the enzyme (amount indicated below) diluted in phosphate buffer 0.1M pH 7 (buffer volume such as total reaction mixture volume was 0.5 ml). The reaction mixture was shaken at room temperature and analysed at different times. The reaction mixture was analysed by the gradient HPLC method 1 and by the chiral CE method 2.
Reaction SMILES: [Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:9][CH:8]=1.[N:19]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21][CH:20]=1>>[Br-:1].[C:10]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:11]=[CH:12][C:7]([CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N+:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[CH:21][CH:20]=2)=[CH:8][CH:9]=1
Reactant: BrCCCCCc1ccc(-c2ccccc2)cc1
Reactant: c1ccc2ncccc2c1
Product: [Br-]
Product: c1ccc(-c2ccc(CCCCC[n+]3cccc4ccccc43)cc2)cc1
Temperature: 65 °C
Yield: 64 %

Procedure:
A mixture of 4-(5-bromopentyl)-1,1′-biphenyl (328 mg, 1.08 mmol) and quinoline (1 mL) was heated at 60-70° C. for 12 hrs. The resulting mixture was washed with diethyl ether and then dissolved in water (30 mL). The aqueous solution was extracted with ethyl acetate (30 mL×5). Water was removed by lyophilization to afford 297 mg of the title compound. Yield: 64%. 1H NMR (300 MHz, CDCl3) δ 1.58 (m, 2H), 1.70 (m, 2H), 2.13 (m, 2H), 2.62 (t, J=7.5 Hz, 2H), 5.37 (t, J=7.8 Hz, 2H), 7.14-7.58 (m, 9H), 7.92 (d, J=7.5 Hz, 1H), 8.17 (m, 2H), 8.36 (m, 2H), 9.13 (d, J=8.4 Hz, 1H), 10.33 (d, J=5.4 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3) δ 26.1, 30.3, 30.9, 35.2, 58.1, 118.3, 122.5, 126.8, 126.9, 127.1, 128.7, 128.8, 129.9, 130.1, 131.1, 136.0, 137.5, 138.5, 140.7, 141.0, 147.3, 150.1 ppm.
Reaction SMILES: [NH:1]1[CH2:11][CH2:10][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:3][CH2:2]1.[C:12](O)(=O)C.C=O>[Pd].O>[CH2:8]([O:7][C:5]([CH:4]1[CH2:3][CH2:2][N:1]([CH3:12])[CH2:11][CH2:10]1)=[O:6])[CH3:9]
Reactant: CCOC(=O)C1CCNCC1
Reactant: CC(=O)O
Agent: [Pd]
Agent: C=O
Solvent: O
Product: CCOC(=O)C1CCN(C)CC1
Temperature: 0 °C
Yield: 99.9 %

Procedure:
Ethyl isonipecotate (20) (5.00 g, 31.8 mmol) was dissolved in an ice-cold mixture of glacial acetic acid (3.80 g, 63.6 mmol) and water (11 mL). Then, a 37% aqueous formaldehyde solution (2.85 mL, 38.2 mmol) was added and the reaction mixture was hydrogenated over Pd/C (10%, 338 mg) at 58 psi H2 for 3.5 h at room temperature. The solid was removed by filtration through Celite, which was washed thoroughly with water (50 mL) and the filtrate was adjusted to pH 11 with 1 M NaOH under cooling. The resulting solution was extracted with Et2O (5×100 mL), the combined organic fractions were dried (MgSO4), and the solvent was removed under reduced pressure to provide 21 (5.44 g, quant.) as a colorless liquid that was used for the next step without further purification. 1H NMR (300 MHz, CDCl3): δ=1.25 (t, J=7.1 Hz, 3 H, OCH2CH3), 1.69-2.06 (m, 6 H, 2-Hax, 3-H2, 5-H2, 6-Hax), 2.18-2.32 (m, 1 H, 4-H), 2.27 (s, 3 H, NMe), 2.75-2.87 (m, 2 H, 2-Heq, 6-Heq), 4.13 (q, J=7.1 Hz, 2 H, OCH2CH3) ppm. —13C NMR (75.5 MHz, CDCl3): δ=14.1 (OCH2CH3), 28.2 (C-3, C-5), 40.5 (C-4), 46.3 (NMe), 54.9 (C-2, C-6), 60.2 (OCH2CH3), 175.0 (C═O) ppm. −MS (70 eV, EI): m/z (%)=171 (31) [M]+, 142 (59) [M-CH2CH3]+, 126 (40) [M-OCH2CH3]+, 98 (56) [M-CO2Et]+. —C9H17NO2 (171.24).
Reaction SMILES: [OH:1][C:2]1[C:11]([C:12]([OH:14])=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:15]([OH:17])=[O:16])[CH:8]=2)[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:24](Cl)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.O>CN(C)C=O.CO>[CH2:24]([O:1][C:2]1[C:11]([C:12]([O:14][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:15]([O:17][CH2:5][C:4]3[CH:9]=[CH:10][CH:11]=[CH:2][CH:3]=3)=[O:16])[CH:8]=2)[CH:3]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: ClCc1ccccc1
Reactant: O=C(O)c1ccc2cc(O)c(C(=O)O)cc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CO
Solvent: O
Product: O=C(OCc1ccccc1)c1ccc2cc(OCc3ccccc3)c(C(=O)OCc3ccccc3)cc2c1
Temperature: 100 °C
Yield: 134.8 %

Procedure:
2-Hydroxy-3,6-di-hydroxycarbonylnaphthalene (2.4 g) was dissolved in dimethylformamide (50 g), followed by heating to 100° C. Potassium carbonate (4.6 g) was slowly added and benzyl chloride (4.2 g) was added dropwise. After heating for about 20 hours, the reaction solution was poured into a mixed solution of water (300 g) and methanol (100 g). The deposit was filtered and then washed with water to obtain 3.5 g of 2-benzyloxy-3,6-di-benzyloxycarbonylnaphthalene as whitish yellow powder (DSC analysis value: 100.5° C.).