Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([C:6]([O:8][CH3:9])=[O:7])[CH2:5][CH:4]=[CH:3][CH2:2]1.O=[O+][O-].[NH2:13][C@H:14]1[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16][CH2:15]1.CCN(CC)CC.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.CO.ClCCCl.C(O)(=O)C>[CH3:9][O:8][C:6]([CH:1]1[CH2:2][CH2:3][N:13]([C@H:14]2[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16][CH2:15]2)[CH2:4][CH2:5]1)=[O:7]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H](N)CC1
Reactant: COC(=O)C1CC=CC1
Agent: O=C([O-])[O-]
Agent: O=[O+][O-]
Agent: [Na+]
Solvent: CO
Solvent: ClCCCl
Solvent: CC(=O)O
Product: COC(=O)C1CCN([C@H]2CCCN(C(=O)OC(C)(C)C)CC2)CC1
Temperature: -78 °C
Reaction time: 3 h
Yield: 64.6 %

Procedure:
Methyl cyclopent-3-ene-1-carboxylate (4.42 g, 35 mmol) was dissolved in DCM/MeOH (160 mL, 3:1) and cooled to −78° C. Ozone was passed through the solution until a blue colour persisted. Excess ozone was purged from the reaction mixture with dry N2. Dimethylsulfide (10 mL) was added and the reaction mixture was warmed to rt, the solvent was removed in vacuo. The residue was added to a solution of tert-butyl (4S)-4-aminoazepane-1-carboxylate (7.5 g, 35 mmol), STAB (18.57 g, 87.6 mmol), NEt3 (4.26 g, 42.1 mmol) and acetic acid (1.8 mL) in DCE (200 mL). The mixture was stirred for 3 hours at rt and was then poured into aqueous Na2CO3 solution. The mixture was extracted with EtOAc (3×200 mL), the organic phase were washed with water (100 mL) and brine (100 mL), dried over Na2SO4. The solvent was removed in vacuo, and the residue was purified by column chromatography (gradient 0% to 25% EtOAc in Petroleum ether) to give tert-butyl (4S)-4-[4-(methoxycarbonyl)piperidin-1-yl]azepane-1-carboxylate (7.7 g, 64.6% yield) as a yellow oil.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][O:8][CH2:9][CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[Br:16][C:17]1[S:26][C:20]2[N:21]=[C:22](Cl)[N:23]=[CH:24][C:19]=2[C:18]=1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.C(Cl)Cl>[Br:16][C:17]1[S:26][C:20]2[N:21]=[C:22]([N:13]3[CH2:14][CH2:15][CH:10]([CH2:9][O:8][CH2:7][CH2:6][N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)[CH2:11][CH2:12]3)[N:23]=[CH:24][C:19]=2[C:18]=1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: Clc1ncc2c(-c3ccccc3)c(Br)sc2n1
Reactant: C1CCN(CCOCC2CCNCC2)C1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CC#N
Product: Brc1sc2nc(N3CCC(COCCN4CCCC4)CC3)ncc2c1-c1ccccc1
Yield: 42.9 %

Procedure:
4-(2-Pyrrolidin-1-ylethoxymethyl)piperidine (0.567 g, 1.74 mmol), 6-bromo-2-chloro-5-phenyl-thieno[2,3-d]pyrimidine (0.554 g, 2.61 mmol) and potassium carbonate (7.21 g, 7.7 mmol) were combined and heated in acetonitrile for 30 minutes to 150° C. in the microwave. The reaction mixture was diluted with DCM, washed with water, dried over Na2SO4 and concentrated at reduced pressure. The resulting residue was purified by flash chromatography, eluting with DCM—92/8/2 DCM/MeOH/NH4OH gradient to afford 6-bromo-5-phenyl-2-[4-(2-pyrrolidin-1-ylethoxymethyl)-1-piperidyl]thieno[2,3-d]pyrimidine (374 mg). LCMS [M+H]+=501.1
Reaction SMILES: [CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[F:19])=[N:5][CH2:4][CH:3]1[CH2:20]Cl.[CH3:22][O:23][C:24](=[O:34])[C@@H:25]([NH2:33])[CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>CN(C)C=O>[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[C:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[F:19])=[N:5][CH2:4][CH:3]1[CH2:20][NH:33][C@H:25]([C:24]([O:23][CH3:22])=[O:34])[CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: CN1c2ccccc2C(c2ccccc2F)=NCC1CCl
Reactant: COC(=O)[C@@H](N)Cc1ccccc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)[C@H](Cc1ccccc1)NCC1CN=C(c2ccccc2F)c2ccccc2N1C
Temperature: 60 °C

Procedure:
1-Methyl-2-chloromethyl-5-(2'-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine (150 mg, 0.5 mmole) and methyl-2(S)-amino-3-phenylpropionate (108 mg, 0.5 mmole) were combined in 4 ml of dry N,N-dimethylformamide, and potassium carbonate (138 mg, 1 mmole) and sodium iodide (70 mg, 0.5 mmole) were added to this mixture. The reaction mixture was protected from moisture and heated at 60° C. for 48 hours. The solvent was then removed under reduced pressure and the residue was partitioned between ethyl acetate (100 ml) and saturated sodium bicarbonate solution (50 ml). The phases were separated and the organic layer was washed with sodium bicarbonate solution and brine, then dried (MgSO4) and concentrated to yield 300 mg of crude product. The analytical product was obtained via chromatography on silica gel (ethyl acetate-hexane elution, 7:3 v/v) as a mixture of diasteriomers; 95% pure by HPLC.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:12]2[CH:17]=[C:16]([O:18]C)[C:15]([Cl:20])=[CH:14][C:13]=2[F:21])=[N:4][N:5]([CH3:11])[C:6]=1[C:7]([F:10])([F:9])[F:8].B(Br)(Br)Br.O>C(Cl)Cl>[Cl:1][C:2]1[C:3]([C:12]2[CH:17]=[C:16]([OH:18])[C:15]([Cl:20])=[CH:14][C:13]=2[F:21])=[N:4][N:5]([CH3:11])[C:6]=1[C:7]([F:9])([F:8])[F:10]
Reactant: COc1cc(-c2nn(C)c(C(F)(F)F)c2Cl)c(F)cc1Cl
Agent: BrB(Br)Br
Solvent: O
Solvent: ClCCl
Product: Cn1nc(-c2cc(O)c(Cl)cc2F)c(Cl)c1C(F)(F)F
Temperature: 25 °C
Reaction time: 6 h
Yield: 96 %

Procedure:
1.39 g of 4-chloro-3-(4-chloro-2-fluoro-5-methoxyphenyl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole was dissolved in 80 ml of anhydrous methylene chloride and then cooled with a dry ice/acetone bath and 0.14 ml of boron tribromide added. After allowing to warm to room temperature, the mixture was treated with an additional 0.28 ml of boron tribromide. Added was an additional 1.0 ml of boron tribromide and stirred at room temperature for 6 hours. After stirring, 30-50 ml of ice cooled water was added and the mixture stirred for 10 minutes. The organic phase was extracted with water, dried with anhydrous magnesium sulfate, filtered and concentrated to give 1.28 g of 4-chloro-3-(4-chloro-2-fluoro-5-hydroxyphenyl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole, m.p. 123.0°-126.0° C.
Reaction SMILES: O.OC1C2N=NNC=2C=CC=1.[C:12]1([C:18]2([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:26]3[CH:22]([CH2:23][NH:24][CH2:25]3)[S:21](=[O:27])[CH2:20][CH2:19]2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[N:34]1([CH2:39][CH:40]([O:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=2[CH2:49][C:50](O)=[O:51])[CH3:41])[CH2:38][CH2:37][CH2:36][CH2:35]1.Cl.CN(C)CCCN=C=NCC>ClCCl>[N:34]1([CH2:39][CH:40]([O:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=2[CH2:49][C:50]([N:24]2[CH2:25][CH:26]3[C:18]([C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=4)([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[CH2:19][CH2:20][S:21](=[O:27])[CH:22]3[CH2:23]2)=[O:51])[CH3:41])[CH2:35][CH2:36][CH2:37][CH2:38]1
Reactant: O=S1CCC(c2ccccc2)(c2ccccc2)C2CNCC21
Reactant: CC(CN1CCCC1)Oc1ccccc1CC(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: Oc1cccc2[nH]nnc12
Solvent: O
Solvent: ClCCl
Product: CC(CN1CCCC1)Oc1ccccc1CC(=O)N1CC2C(C1)C(c1ccccc1)(c1ccccc1)CCS2=O
Temperature: 20 °C
Reaction time: 20 h
Yield: 36.5 %

Procedure:
0.03 g of hydroxybenzotriazole hydrate is added to a solution, cooled to +5° C., of 0.69 g of (1RS,4aRS,7aRS)-4,4-diphenylperhydrothiopyrano[2,3-c]pyrrole 1-oxide and 0.68 g of {[3-(1-pyrrolidinyl)-2-propoxy]phenyl}acetic acid in 25 cm3 of dry dichloromethane, followed by a solution of 0.5 g of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in 20 cm3 of dry dichloromethane. After stirring for 2 hours at +5° C. and 20 hours at 20° C., the reaction mixture is washed twice with 50 cm3 of distilled water and dried over magnesium sulphate and then concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 2.4 cm, height 32 cm), eluting under a nitrogen pressure of 0.8 bar with an ethyl acetate, acetic acid and water mixture (80/20/20 by volume) and collecting fractions of 25 cm3. Fractions 21 to 50 are pooled and concentrated to dryness under reduced pressure (2.7 kPa). The residue is crystallized from 8 cm3 of ethyl acetate, the crystals are washed with ethyl acetate and diisopropyl oxide and then dried. 0.45 g of (1RS,4aRS,7aRS)-6-{{[3-(1-pyrrolidinyl)-2-propoxy]phenyl}acetyl}-4,4-diphenylperhydrothiopyrano[2,3-c]-pyrrole 1-oxide is obtained in the form of beige crystals; melting point 126° C.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Br[CH2:10][CH2:11][S:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[C:15]([F:20])[CH:14]=1.[OH:21][CH:22]([C:35]1[C:44]2[C:39](=[CH:40][CH:41]=[C:42]([O:45][CH3:46])[CH:43]=2)[N:38]=[CH:37][CH:36]=1)[CH2:23][CH2:24][C@@H:25]1[CH2:30][CH2:29][NH:28][CH2:27][C@@H:26]1[C:31]([O:33][CH3:34])=[O:32]>C(#N)C.CO>[F:20][C:15]1[CH:14]=[C:13]([S:12][CH2:11][CH2:10][N:28]2[CH2:29][CH2:30][C@@H:25]([CH2:24][CH2:23][CH:22]([OH:21])[C:35]3[C:44]4[C:39](=[CH:40][CH:41]=[C:42]([O:45][CH3:46])[CH:43]=4)[N:38]=[CH:37][CH:36]=3)[C@@H:26]([C:31]([O:33][CH3:34])=[O:32])[CH2:27]2)[CH:18]=[C:17]([F:19])[CH:16]=1
Reactant: COC(=O)[C@H]1CNCC[C@H]1CCC(O)c1ccnc2ccc(OC)cc12
Reactant: Fc1cc(F)cc(SCCBr)c1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Solvent: CO
Product: COC(=O)[C@H]1CN(CCSc2cc(F)cc(F)c2)CC[C@H]1CCC(O)c1ccnc2ccc(OC)cc12
Temperature: 80 °C
Yield: 44.3 %

Procedure:
0.332 g of potassium carbonate, then 0.4 g of potassium iodide and, finally, 0.675 g of 1-[(2-bromoethyl)thio]-3,5-difluorobenzene, dissolved beforehand in 5 cm3 of acetonitrile, were added at a temperature in the region of 20° C., with stirring and under an inert atmosphere, to a solution of 0.717 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate in 15 cm3 of acetonitrile and 1 cm3 of methanol. The mixture was heated for 3 hours at a temperature in the region of 80° C. After cooling to a temperature in the region of 20° C., the reaction mixture was filtered and the cake was washed with 2 times 5 cm3 of acetonitrile. The filtrate was evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was purified by chromatography under a nitrogen pressure of 50 kPa on a column of silica gel (particle size 40-63 μm; diameter 3.5 cm; height 35 cm), elution was carried out with a dichloromethane/methanol (95/5 by volume) mixture, and 35-cm3 fractions were collected. Fractions 18 to 21 were combined and then evaporated as above. 0.47 g of methyl (3R,4R)-1-[2-(3,5-difluorophenylthio)ethyl]-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin-4-yl)propyl]piperidine-3-carboxylate was obtained in the form of a viscous oil with an orange-yellow color.
Reaction SMILES: C[O:2][C:3](=[O:38])[C:4]([O:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][C:17]2[N:18]=[C:19]([C:26]3[CH:31]=[CH:30][C:29]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)=[CH:28][CH:27]=3)[O:20][C:21]=2[C:22]([F:25])([F:24])[F:23])=[CH:10][CH:9]=1)([CH3:6])[CH3:5].[OH-].[Na+].Cl>C(O)C>[C:29]1([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:28]=[CH:27][C:26]([C:19]2[O:20][C:21]([C:22]([F:25])([F:24])[F:23])=[C:17]([CH2:16][CH2:15][O:14][C:11]3[CH:12]=[CH:13][C:8]([O:7][C:4]([CH3:6])([CH3:5])[C:3]([OH:38])=[O:2])=[CH:9][CH:10]=3)[N:18]=2)=[CH:31][CH:30]=1
Reactant: COC(=O)C(C)(C)Oc1ccc(OCCc2nc(-c3ccc(-c4ccccc4)cc3)oc2C(F)(F)F)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CC(C)(Oc1ccc(OCCc2nc(-c3ccc(-c4ccccc4)cc3)oc2C(F)(F)F)cc1)C(=O)O
Temperature: 50 °C
Reaction time: 1 h

Procedure:
A sample of 2-{4-[2-(2-biphenyl-4-yl-5-trifluoromethyloxazol-4-yl)-ethoxy]-phenoxy}-2-methyl-propionic acid methyl ester (141 mg, 0.21 mmol) was dissolved in ethanol (2 mL) followed by addition of 5.0 N NaOH (0.6 mL). The mixture was warmed with magnetic stirring at 50° C. for one hour. The reaction mixture was then allowed to cool to room temperature then acidified with 1.0 N HCl (3 mL) then extracted with methylene chloride (50 mL). The organic phase was separated, dried over sodium chloride and concentrated under reduced pressure to yield 134 mg (98%, 24% overall) of a glassy solid. HPLC RT1=5.90 min; 1H NMR (400 MHz, CDCl3) δ8.08 (d, J=8.3 Hz, 2H), 7.67 (d, J=8.3 Hz, 2H), 7.60 (d, J=8.3 Hz, 2H), 7.45-7.36 (m, 3H), 6.86 (d, J=9.3 Hz, 2H), 6.78 (d, J=9.3 Hz, 2H), 4.24 (t, J=6.3 Hz, 2H), 3.15 (t, J=6.3 Hz, 2H), 1.48 (s, 6H); MS (EI) 511.95 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][C:5]([C:11]([F:14])([F:13])[F:12])=[CH:4][C:3]=1[N+:15]([O-])=O>C1(C)C=CC=CC=1>[NH2:15][C:3]1[CH:4]=[C:5]([C:11]([F:14])([F:12])[F:13])[CH:6]=[C:7]([NH2:8])[C:2]=1[Cl:1]
Reactant: O=[N+]([O-])c1cc(C(F)(F)F)cc([N+](=O)[O-])c1Cl
Solvent: Cc1ccccc1
Product: Nc1cc(C(F)(F)F)cc(N)c1Cl
Yield: 95.7 %

Procedure:
40 g of 4-chloro-3,5-dinitro-benzotrifluoride and 47 g of toluene are placed in an agitator autoclave, and the catalyst suspension is flushed in with 4 g of water. Hydrogenation subsequently takes place at a temperature of 100° C. and at a hydrogen pressure of 5 bar. When the hydrogen uptake is complete, the autoclave is cooled and rendered inert with nitrogen. The catalyst is filtered off and washed with toluene. After working up by distillation, 29.8 g of 3,5-diamino-4-chloro-benzotrifluoride (yield 95.8% of theory) are obtained. Elementary analysis:
Reaction SMILES: [C:1]1([CH3:26])[CH:6]=[C:5]([CH3:7])[CH:4]=[C:3]([CH3:8])[C:2]=1[S:9]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C:19]1[C:20](=O)[CH2:21][CH2:22][C:23]=1[CH3:24])(=[O:11])=[O:10].[CH2:27]1COCC1.[Li]C.C([O-])(O)=O.[Na+]>O>[CH3:24][C:23]1[CH2:22][CH:21]=[C:20]([CH3:27])[C:19]=1[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[NH:12][S:9]([C:2]1[C:3]([CH3:8])=[CH:4][C:5]([CH3:7])=[CH:6][C:1]=1[CH3:26])(=[O:11])=[O:10]
Reactant: C1CCOC1
Reactant: CC1=C(c2ccccc2NS(=O)(=O)c2c(C)cc(C)cc2C)C(=O)CC1
Agent: O=C([O-])O
Agent: [Li]C
Agent: [Na+]
Solvent: O
Product: CC1=CCC(C)=C1c1ccccc1NS(=O)(=O)c1c(C)cc(C)cc1C
Temperature: -78 °C
Reaction time: 2 h

Procedure:
0.645 g (1.746 mmol) of 2-(2-(2-mesitylenesulfonyl)aminophenyl)-3-methyl-2-cyclopenten-1-one and 12 mL of THF were loaded to a 50 mL flask, and then 2.30 mL (3.677 mmol) of MeLi (1.6 M in diethyl ether) was added thereto at −78° C. and stirred at the same temperature for two hours. The reaction product was stirred for 2 hours while the temperature was slowly raised. 10 mL of distilled water was added to the resultant reaction product and the THF contained therein was removed using a rotary vacuum evaporator. 10 mL of E.A and 5 mL of 2 N HCl were added to the reaction product from which the THF had been removed and strongly stirred for 3 minutes. Subsequently, the organic layer was collected from the stirred reaction product. 5 mL of E.A was twice added to the aqueous layer to obtain the organic layer. The collected organic layer was neutralized using 5 mL of NaHCO3 and dried over MgSO4 to remove water contained therein. The solvent contained in the dried product was removed using a rotary vacuum evaporator. The product was filtered using a column chromatography (hexane:E.A=10:1) (0.550 g, 88%).
Reaction SMILES: [O:1]=[CH:2][C@H:3]([C@@H:5]([C@@H:7]([CH2:9][OH:10])[OH:8])[OH:6])[OH:4].N1C=CN=C1.[C:16]([Si:20]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)Cl)([CH3:19])([CH3:18])[CH3:17]>CN(C)C=O>[Si:20]([O:1][CH2:2][C@H:3]1[O:4][CH:9]([OH:10])[C@@H:7]([OH:8])[C@@H:5]1[OH:6])([C:16]([CH3:19])([CH3:18])[CH3:17])([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: O=C[C@@H](O)[C@H](O)[C@H](O)CO
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](OC[C@H]1OC(O)[C@@H](O)[C@@H]1O)(c1ccccc1)c1ccccc1
Reaction time: 0.5 h

Procedure:
D-Arabinose (200 g) and imidazole (199 g) were placed in a three-neck round bottom flask and connected to high vacuum for 30 minutes. The vacuum was released under nitrogen atmosphere and dimethylformamide (1.8 L) was added to the above mixture at room temperature followed by drop-wise addition of t-butyldiphenylchlorosilane (443 mL) for 10 minutes under a nitrogen atmosphere. The resulting mixture was stirred for 16 hours at the same temperature. Dimethylformamide was evaporated under reduced pressure. The residue was taken up in ethyl acetate and washed with water. The organic layer was dried over anhydrous sodium sulphate. The solvent was evaporated under reduced pressure to obtain a crude residue which was purified by column chromatography over silica gel using 80% ethyl acetate in hexane as eluant to afford the title compound (273 g).
Reaction SMILES: [C@@H:1]1([OH:7])[CH2:5][CH2:4][CH2:3][C@@H:2]1[OH:6].F[C:9]1[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=1[N+:16]([O-:18])=[O:17]>>[F:15][C:13]1[CH:12]=[CH:11][C:10]([N+:16]([O-:18])=[O:17])=[C:9]([CH:14]=1)[O:6][C@H:2]1[CH2:3][CH2:4][CH2:5][C@H:1]1[OH:7]
Reactant: O=[N+]([O-])c1ccc(F)cc1F
Reactant: O[C@@H]1CCC[C@@H]1O
Product: O=[N+]([O-])c1ccc(F)cc1O[C@H]1CCC[C@H]1O

Procedure:
Prepared analogously to III.1 from cis-1,2-cyclopentandiol (1.0 g) and 1.28 ml 2,4-difluoronitrobenzene.
Reaction SMILES: C(O)(C(F)(F)F)=O.C(OC([N:15]1[CH2:20][CH2:19][CH:18]([C:21]2[C:29]3[C:24](=[CH:25][CH:26]=[C:27]([C:30]([O:32][CH3:33])=[O:31])[CH:28]=3)[NH:23][CH:22]=2)[CH2:17][CH2:16]1)=O)(C)(C)C>C(Cl)Cl>[NH:15]1[CH2:16][CH2:17][CH:18]([C:21]2[C:29]3[C:24](=[CH:25][CH:26]=[C:27]([C:30]([O:32][CH3:33])=[O:31])[CH:28]=3)[NH:23][CH:22]=2)[CH2:19][CH2:20]1
Reactant: COC(=O)c1ccc2[nH]cc(C3CCN(C(=O)OC(C)(C)C)CC3)c2c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)c1ccc2[nH]cc(C3CCNCC3)c2c1
Reaction time: 0.5 h
Yield: 81.5 %

Procedure:
TFA (10 mL) was added in one portion at ambient temperature to a stirred solution of methyl 3-[1-(tert-butoxycarbonyl)piperidin-4-yl]-1H-indole-5-carboxylate (4.58 g, 12.78 mmol) in DCM (30 mL). The resulting solution was stirred for 30 minutes then applied to an SCX column and eluted with methanol followed by 2M ammonia in methanol. Pure fractions were combined and concentrated by evaporation then triturated with ether to give a solid which was collected by filtration and air dried to give methyl 3-(piperidin-4-yl)-1H-indole-5-carboxylate (2.69 g, 81%) as a pale yellow solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([O:13][CH3:14])=[CH:5][CH:4]=1.[C:15](Cl)(=[O:18])[CH2:16][CH3:17].[Cl-].[Al+3].[Cl-].[Cl-].O>ClC(Cl)C>[CH3:14][O:13][C:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]([O:2][CH3:1])=[CH:4][C:5]=1[C:15](=[O:18])[CH2:16][CH3:17]
Reactant: CCC(=O)Cl
Reactant: COc1ccc(OC)c2ccccc12
Agent: [Al+3]
Agent: [Cl-]
Solvent: CC(Cl)Cl
Solvent: O
Product: CCC(=O)c1cc(OC)c2ccccc2c1OC
Temperature: 25 °C
Reaction time: 4 h
Yield: 21.5 %

Procedure:
To a cold solution (ice bath) of 1,4-dimethoxy-naphthalene (5 g, 26.6 mmol) in dichloroethane (100 mL) was added propionyl chloride (2.7 g, 29.3 mmol) followed by aluminum chloride (3.9 g, 29.3 mmol). After the addition was complete, the reaction mixture was allowed to warm to room temperature and stirred for 4 hr. Water (200 mL) was added and the organic material was extracted with dichloromethane (200 mL). The organic extracts were dried (MgSO4) and concentrated to give a residue which was purified by flash chromatography (silica gel, ethyl acetate/hexane: 1/9) to give an oil (1.4 g): 1H NMR (DMSO-d6) δ 1.16 (t, 3H, CH3), 3.13 (q, 2H, CH2), 3.87 (s, 3H, OCH3), 3.98 (s, 3H, OCH3), 7.02 (s, 1H, Ar—H), 7.67 (m, 2H, Ar—H), 8.10 (d, 2H, Ar—H); MS 245 (M+1).
Reaction SMILES: C([O:8][C:9]([C:11]1[N:12]=[C:13]([CH:16]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[CH:25][CH:24]=2)[CH2:17][C:18]([O:20][CH3:21])=[O:19])[O:14][CH:15]=1)=[O:10])C1C=CC=CC=1>CCO.[Pd]>[C:9]([C:11]1[N:12]=[C:13]([CH:16]([CH2:22][C:23]2[CH:24]=[CH:25][C:26]([O:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[CH:27][CH:28]=2)[CH2:17][C:18]([O:20][CH3:21])=[O:19])[O:14][CH:15]=1)([OH:10])=[O:8]
Reactant: COC(=O)CC(Cc1ccc(OC(=O)OC(C)(C)C)cc1)c1nc(C(=O)OCc2ccccc2)co1
Agent: [Pd]
Solvent: CCO
Product: COC(=O)CC(Cc1ccc(OC(=O)OC(C)(C)C)cc1)c1nc(C(=O)O)co1
Yield: 105.6 %

Procedure:
A mixture of methyl (±)-3-[4-(benzyloxycarbonyl)-1,3-oxazol-2-yl]-4-[4-[(tert-butyloxycarbonyl)oxy]phenyl]butanoate (765 mg, 1.54 mmole) and 10% Pd/C (164 mg) in EtOH (20 mL) was deoxygenated (3×evacuation/N2 purge cycles) then was charged with H2 (50 psi). After 4 hr the H2 was removed and the mixture was filtered through a pad of celite®. The filtrate was concentrated to afford the title compound (659 mg, 100%) as a white solid: MS (ES) m/e 811 (2M+H)+.
Reaction SMILES: C=O.C(=O)C.C(=O)CC.N.N1C=CC=C(C)C=1.N1C=C(C)C=C(C)C=1.N1C(C)=CC=CC=1C.[CH2:34]([C:36]1[C:41]([CH3:42])=[CH:40][CH:39]=[C:38]([CH2:43]C)[N:37]=1)C>CC(CC)=O.C(C(CC)=O)C.CC(C)=O.N1C=CC=CC=1>[CH3:34][C:36]1[C:41]([CH3:42])=[CH:40][CH:39]=[C:38]([CH3:43])[N:37]=1
Reactant: CCc1ccc(C)c(CC)n1
Agent: C=O
Agent: CC=O
Agent: Cc1cncc(C)c1
Solvent: Cc1cccc(C)n1
Solvent: CC(C)=O
Solvent: CCC(C)=O
Product: Cc1ccc(C)c(C)n1

Procedure:
Such pyridine bases as pyridine, picoline, lutidine, collidine, etc. can be produced in the present invention. For example, when formaldehyde and acetaldehyde are used together with ammonia, pyridine and 3-picoline are obtained. When formaldehyde and propionaldehyde are used together with ammonia, 3,5-lutidine and a small amount of 3-picoline are obtained. When formaldehyde, acetaldehyde and propionaldehyde are used together with ammonia, pyridine, 3-picoline and 3,5-lutidine are obtained. Further, when formaldehyde and acetone are used together with ammonia, 2,6-lutidine is principally obtained. When diethylketone or methylethylketone is used together with ammonia, 2,6-diethyl-3-methylpyridine or 2,3,6-trimethylpyridine is obtained.
Reaction SMILES: C(O)(=O)C.Cl.Cl.[NH2:7][C@@H:8]1[CH2:13][CH2:12][CH2:11][NH:10][CH2:9]1.[CH3:14][C:15]1[CH:16]=[C:17]2[C:22](=O)[O:21][C:19](=[O:20])[C:18]2=[CH:24][CH:25]=1>CC(C)=O>[CH3:14][C:15]1[CH:16]=[C:17]2[C:22](=[O:21])[N:7]([C@@H:8]3[CH2:13][CH2:12][CH2:11][NH:10][CH2:9]3)[C:19](=[O:20])[C:18]2=[CH:24][CH:25]=1
Reactant: Cc1ccc2c(c1)C(=O)OC2=O
Reactant: N[C@@H]1CCCNC1
Agent: Cl
Solvent: CC(=O)O
Solvent: CC(C)=O
Product: Cc1ccc2c(c1)C(=O)N([C@@H]1CCCNC1)C2=O
Temperature: 27.5 °C

Procedure:
In a clean round bottom flask, 100 ml acetic acid, 50 gms 3-(R)-aminopiperidine dihydrochloride & 56.5 gms of 4-methylphthalic anhydride were charged. The reaction mass was refluxed & then cooled to 25-30° C. Acetone was added to the reaction mass & obtained solid was filtered. Acetone was added to the solid obtained & refluxed to get uniform slurry. The reaction mass was cooled to 25-30° C. & filtered. Wet wt 70 gms. In another round bottom flask, methylene dichloride, wet cake and water were charged. The reaction mass was basified & layers were separated. The organic layer was washed with water & concentrated upto half volume. Diisopropyl ether was added to the reaction mass to obtain the product. Dry wt 40 gms, HPLC purity=85%