Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([C:6]([OH:8])=O)=[CH:2]1.Cl.CN(C)CCCN=C=NCC.[NH:21]1[CH2:31][CH2:30][CH2:29][CH:23]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:22]1>ClCCl>[S:1]1[CH:5]=[CH:4][C:3]([C:6]([N:21]2[CH2:31][CH2:30][CH2:29][CH:23]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:22]2)=[O:8])=[CH:2]1
Reactant: CCOC(=O)C1CCCNC1
Reactant: O=C(O)c1ccsc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: CCOC(=O)C1CCCN(C(=O)c2ccsc2)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 19.1 %

Procedure:
Commercially available 3-thiophene carboxylic acid (166.5 mg; 1.30 mmol) was suspended in dichloromethane (7 ml), and commercially available 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (252.8 mg; 1.32 mmol) was added. This mixture was allowed to stir at ambient temperature for 1 hour. Ethyl nipecotate (201 μl; 1.3 mmol) was then added, and stirring was continued for approximately 18 hours. The reaction mixture was then diluted with fresh dichloromethane and washed with water. The dichloromethane was dried with anhydrous potassium carbonate and evaporated at ambient temperature under reduced pressure. The crude material was purified by high-vacuum distillation at approximately 225° C./0.1 torr, and further by chromatography on silica, eluting with 50% ethyl acetate in hexane, giving ethyl 1-(3-thiophenecarbonyl)-3-piperidinecarboxylate (66.3 mg) as a colorless oil. MS m/z (positive ion) 268 (MH+; 100).
Reaction SMILES: [I-].[C:2]([C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][CH:10]=[N+:11]2[CH2:14][CH:15]=[CH2:16])=[CH:6][CH:5]=1)#[N:3].[OH-:17].[K+].O>O1CCOCC1.O.[Fe-3](C#N)(C#N)(C#N)(C#N)(C#N)C#N.[K+].[K+].[K+]>[O:17]=[C:10]1[CH:9]=[CH:8][C:7]2[C:12](=[CH:13][C:4]([C:2]#[N:3])=[CH:5][CH:6]=2)[N:11]1[CH2:14][CH:15]=[CH2:16]
Reactant: [OH-]
Reactant: C=CC[n+]1cccc2ccc(C#N)cc21
Agent: N#C[Fe-3](C#N)(C#N)(C#N)(C#N)C#N
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: C=CCn1c(=O)ccc2ccc(C#N)cc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 52.9 %

Procedure:
A mixture of 7-cyano-1-(2-propen-1-yl)quinolinium iodide (1.75 g, 5.4 mmol), potassium hydroxide (1.33 g, 23.76 mmol) and potassium ferricyanide (3.9 g, 11.9 mmol) in 50% 1,4-dioxane/water was stirred at rt for 2 h. Water (50 ml) was then added and the organic phase was extracted with 10% methanol/DCM (2×100 ml). The combined organic phases were washed with water (100 ml) then dried and evaporated. The residue was chromatographed on silica gel, eluting with 0-5% methanol-DCM to afford the desired compound (0.6 g, 55%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][OH:10])[CH:5]=[CH:6][CH:7]=1.[C:11](OC(=O)C)(=[O:13])[CH3:12].[Li+].[OH-]>C(O)(=O)C>[OH:10][CH2:9][CH2:8][C:4]1[CH:3]=[C:2]([NH:1][C:11](=[O:13])[CH3:12])[CH:7]=[CH:6][CH:5]=1
Reactant: Nc1cccc(CCO)c1
Reactant: CC(=O)OC(C)=O
Agent: [Li+]
Agent: [OH-]
Solvent: CC(=O)O
Product: CC(=O)Nc1cccc(CCO)c1
Temperature: 110 °C
Reaction time: 8 h

Procedure:
To a vial containing 2-(3-aminophenyl)ethanol (137.0 mg, 1.0 mmol) in glacial acetic acid (3 mL) was added acetic anhydride (1 mL). The reaction vial was sealed and heated at 110° C. for 6 h. The mixture was concentrated under reduced pressure. The crude product was dissolved in MeOH (3 mL) and LiOH (120.0 mg, 5.0 mmol) was added. The solution was allowed to stir overnight at rt. The solution was concentrated under reduced pressure and diluted with ethyl acetate. The organic phase was washed with water (2×5 mL), brine and dried (Na2SO4). The solvent was removed under reduced pressure and the crude mixture was purified by column chromatography to afford the desired product in 39%. 1H NMR: 1.65 (t, 1H, J=6.0 Hz), 2.13 (s, 3H), 2.81 (t, 2H, J=6.4 Hz), 3.81 (q, 2H, J=6.0 Hz), 6.94 (t, 1H, J=6.8 Hz), 7.22 (t, 1H, J=7.6 Hz), 7.30-7.40 (m, 3H).
Reaction SMILES: [CH3:1][N:2]([CH3:28])[C:3]([C:5]1[N:22]([CH:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)[C:8]2[N:9]=[C:10]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([CH:20]=O)=[CH:16][N:15]=3)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4].[CH3:29][N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1>>[CH3:1][N:2]([CH3:28])[C:3]([C:5]1[N:22]([CH:23]2[CH2:27][CH2:26][CH2:25][CH2:24]2)[C:8]2[N:9]=[C:10]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([CH2:20][N:33]4[CH2:34][CH2:35][N:30]([CH3:29])[CH2:31][CH2:32]4)=[CH:16][N:15]=3)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4]
Reactant: CN1CCNCC1
Reactant: CN(C)C(=O)c1cc2cnc(Nc3ccc(C=O)cn3)nc2n1C1CCCC1
Product: CN1CCN(Cc2ccc(Nc3ncc4cc(C(=O)N(C)C)n(C5CCCC5)c4n3)nc2)CC1

Procedure:
Following General Procedure B, 7-cyclopentyl-2-(5-formyl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (0.2 g, 0.529 mmol) and N-methyl piperazine (58 mg, 0.582 mmol) gave 7-cyclopentyl-2-[5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-ylamino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide as a white off solid (0.144 g, 60%) [following further purification by SiO2 chromatography, eluting with 2-5% (2N NH3 in MeOH/dichloromethane]. MS (ESI) m/z 463.3 (M+H)+ (method B).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH:24]=[CH:23]2)=[C:6]([CH:20]=1)[CH2:7][N:8]([C:11]1[N:16]=[N:15][C:14]([C:17]([OH:19])=O)=[CH:13][CH:12]=1)[CH2:9][CH3:10].[CH3:28][C:29]1[C:33]([S:34]([NH2:37])(=[O:36])=[O:35])=[C:32]([CH3:38])[O:31][N:30]=1>>[CH3:28][C:29]1[C:33]([S:34]([NH:37][C:17]([C:14]2[N:15]=[N:16][C:11]([N:8]([CH2:7][C:6]3[CH:20]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=3[O:21][CH:22]3[CH2:27][CH2:26][CH2:25][CH:24]=[CH:23]3)[CH2:9][CH3:10])=[CH:12][CH:13]=2)=[O:19])(=[O:36])=[O:35])=[C:32]([CH3:38])[O:31][N:30]=1
Reactant: CCN(Cc1cc(Cl)ccc1OC1C=CCCC1)c1ccc(C(=O)O)nn1
Reactant: Cc1noc(C)c1S(N)(=O)=O
Product: CCN(Cc1cc(Cl)ccc1OC1C=CCCC1)c1ccc(C(=O)NS(=O)(=O)c2c(C)noc2C)nn1

Procedure:
The title compound was prepared from 6-[N-(5-chloro-2-(cyclohexen-3-yloxy)benzyl)-N-ethylamino]pyridazine-3-carboxylic acid (example 23) and 3,5-dimethylisoxazol-4-ylsulphonamide using a similar method to that of example 11 (Yield 22%).
Reaction SMILES: [O:1]=[C:2]1[NH:8][C:7]2[N:9]=[CH:10][CH:11]=[CH:12][C:6]=2[CH2:5][CH2:4][N:3]1[CH:13]1[CH2:18][CH2:17][N:16](C(OC(C)(C)C)=O)[CH2:15][CH2:14]1.FC(F)(F)C(O)=O.[ClH:33].C(OCC)C>ClCCl>[ClH:33].[ClH:33].[NH:16]1[CH2:15][CH2:14][CH:13]([N:3]2[CH2:4][CH2:5][C:6]3[CH:12]=[CH:11][CH:10]=[N:9][C:7]=3[NH:8][C:2]2=[O:1])[CH2:18][CH2:17]1
Reactant: CC(C)(C)OC(=O)N1CCC(N2CCc3cccnc3NC2=O)CC1
Agent: Cl
Solvent: CCOCC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C1Nc2ncccc2CCN1C1CCNCC1
Temperature: 25 °C
Reaction time: 4 h
Yield: 99 %

Procedure:
tert-Butyl 4-(2-oxo-4,5-dihydro-1H-pyrido[2,3-d][1,3]diazepin-3(2H)-yl)piperidine-1-carboxylate (0.51 g, 1.472 mmol) was dissolved in dichloromethane (8 ml). Trifluoroacetic acid (2 ml, 26.0 mmol) was added to the solution. The mixture was stirred at room temperature for 4 hours. All volatiles were removed by roto-vap. Residue was dissolved in dichloromethane (10 mL). 2M Hydrogen chloride in diethyl ether (2.58 ml, 5.15 mmol) was added to the mixture. The mixture was stirred at room temperature for 15 minutes and then all volatiles were removed. The resulting off-white solid was washed with anhydrous diethyl ether four times to afford the title compound as white solid in 99% yield. 1H NMR (500 MHz, D2O) δ ppm 8.01-8.29 (m, 2 H) 7.38 (t, J=6.71 Hz, 1 H) 4.63-4.88 (m, 2 H) 4.29-4.53 (m, 1 H) 3.61-3.71 (m, 2 H) 3.45-3.62 (m, 2 H) 3.01-3.27 (m, 4 H) 1.93-2.21 (m, 4 H).
Reaction SMILES: O.[NH2:2][NH2:3].[NH2:4][C:5]1[C:6]([C:11]([O:13]C)=O)=[N:7][CH:8]=[CH:9][N:10]=1>C(O)C>[NH2:4][C:5]1[C:6]([C:11]([NH:2][NH2:3])=[O:13])=[N:7][CH:8]=[CH:9][N:10]=1
Reactant: COC(=O)c1nccnc1N
Reactant: NN
Solvent: CCO
Solvent: O
Product: NNC(=O)c1nccnc1N
Temperature: 60 °C
Reaction time: 2 h
Yield: 97.4 %

Procedure:
Hydrazine monohydrate (34 mL, 1094.95 mmol) was added portionwise to a stirred suspension of methyl 3-aminopyrazine-2-carboxylate (21.3 g, 139.09 mmol) in ethanol (65 mL) at r.t. The resulting slurry was stirred at 60° C. for 2 hours, cooled to room temperature and filtered. The solid was washed with cold ethanol (2×25 ml) and dried to a constant weight to afford 3-aminopyrazine-2-carbohydrazide (20.75 g, 97%) as a beige solid: 1H NMR Spectrum; (DMSO-d6) 4.49 (2H, d), 7.46 (2H, br s), 7.78 (1H, d), 8.17 (1H, d), 9.79 (1H, t); Mass Spectrum [M+H]+=154.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:10]2[N:14]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([Cl:21])[CH:16]=3)[N:13]=[C:12]([C:22](O)=[O:23])[CH:11]=2)[CH:5]=[C:6]([O:8][CH3:9])[CH:7]=1.ClC1C=C(C2N(C3C=CC=CN=3)N=C([C:44]([N:46]3[CH2:50][C:49](=[O:51])[NH:48][CH2:47]3)=O)C=2)C=C(F)C=1.O=C1CNCCN1>>[Br:1][C:2]1[CH:3]=[C:4]([C:10]2[N:14]([C:15]3[CH:20]=[CH:19][N:18]=[C:17]([Cl:21])[CH:16]=3)[N:13]=[C:12]([C:22]([N:46]3[CH2:44][CH2:47][NH:48][C:49](=[O:51])[CH2:50]3)=[O:23])[CH:11]=2)[CH:5]=[C:6]([O:8][CH3:9])[CH:7]=1
Reactant: COc1cc(Br)cc(-c2cc(C(=O)O)nn2-c2ccnc(Cl)c2)c1
Reactant: O=C1CN(C(=O)c2cc(-c3cc(F)cc(Cl)c3)n(-c3ccccn3)n2)CN1
Agent: O=C1CNCCN1
Product: COc1cc(Br)cc(-c2cc(C(=O)N3CCNC(=O)C3)nn2-c2ccnc(Cl)c2)c1

Procedure:
50 mg (0.12 mmol) of the compound of Example 51A is reacted analogously to the synthesis of the compound of Example 1 with 13 mg (0.14 mmol) of 2-oxopiperazine. 50 mg (84% of theory) of the title compound is obtained.
Reaction SMILES: [C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2].[Li]CCCC.[C:21]1([C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH3:35])=[O:28])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[NH4+].[Cl-]>C1COCC1.O.CCOC(C)=O>[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:13]=[C:12]([CH2:14][C:27]([OH:28])([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH3:35])[CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1ccccc1C(=O)c1ccccc1
Reactant: Cc1ccnc(NC(=O)OC(C)(C)C)c1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: Cc1ccccc1C(O)(Cc1ccnc(NC(=O)OC(C)(C)C)c1)c1ccccc1
Temperature: -78 °C
Reaction time: 0.25 h
Yield: 63.7 %

Procedure:
(4-Methyl-pyridin-2-yl)-carbamic acid tert-butyl ester (300 mg, 1.4 mmol) is dissolved in dry THF (15 mL) and it is cooled down to −78° C. After 1.6 M n-BuLi (4.5 mL, 7.2 mmol) is added at −78° C., the cooling bath is removed and the mixture is stirred at room temperature for 15 min. Then the reaction mixture is cooled down to −78° C. again and phenyl-o-tolyl-methanone (1.3 mL, 7.2 mmol) is added. After the mixture is stirred for 30 min at −78° C., saturated NH4Cl aqueous solution (15 mL) is added and the reaction is warmed up to room temperature. EtOAc (60 mL) is added along with water (50 mL). The mixture is stirred for another 10 min and the aqueous layer is separated, extracted with EtOAc (2×35 ml). The organic layers are combined and concentrated to give the crude product. Purification by silica flash column chromatography using MeOH in DCM (gradient from 0% to 10%) affords 361 mg of the desired product.
Reaction SMILES: F[C:2](F)(F)[C:3]([OH:5])=O.C([NH:15][C:16]1[CH:40]=[CH:39][C:19]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:33][CH2:34][C:35](F)(F)F)=[C:28]([O:31][CH3:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)=[CH:18][CH:17]=1)(OC(C)(C)C)=O>ClCCl>[NH2:15][C:16]1[CH:40]=[CH:39][C:19]([NH:20][C:21]2[C:30]3[C:25](=[CH:26][C:27]([O:33][CH2:34][CH2:35][CH2:21][N:20]4[CH2:2][CH2:3][O:5][CH2:18][CH2:19]4)=[C:28]([O:31][CH3:32])[CH:29]=3)[N:24]=[CH:23][N:22]=2)=[CH:18][CH:17]=1
Reactant: COc1cc2c(Nc3ccc(NC(=O)OC(C)(C)C)cc3)ncnc2cc1OCC(F)(F)F
Reactant: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1cc2c(Nc3ccc(N)cc3)ncnc2cc1OCCCN1CCOCC1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 234.6 %

Procedure:
Trifluoroacetic acid (20.0 ml, 260 mmol) was added to a suspension of 4-(4-(N-Boc-amino)anilino)-6-methoxy-7-(2,2,2-trifluoroethoxy)quinazoline (7.50 g, 11.7 mmol) in dichloromethane (80 ml) and the reaction stirred for 45 minutes at ambient temperature. The solvents were removed in vacuo, the residue was suspended in water (50 ml) and saturated aqueous sodium bicarbonate solution was added. The aqueous phase was extracted with ethyl acetate (3×100 ml) and the combined organic layers were washed with brine (100 ml) and evaporated in vacuo. Drying of the solid in vacuo yielded 4-(4-aminoanilino)-6-methoxy-7-(3-morpholinopropoxy)quinazoline (5.62 g, 100% yield) as a yellow solid:
Reaction SMILES: [CH2:1]([N:8]([CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:9]1([C:13]#[N:14])[CH2:12][O:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1CC(=O)C1.C(NCC1C=CC=CC=1)C1C=CC=CC=1.C[Si](C#N)(C)C>CO.[Ni]>[NH2:14][CH2:13][C:9]1([N:8]([CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:12][O:11][CH2:10]1
Reactant: N#CC1(N(Cc2ccccc2)Cc2ccccc2)COC1
Agent: [Ni]
Agent: C[Si](C)(C)C#N
Agent: O=C1COC1
Solvent: CO
Product: NCC1(N(Cc2ccccc2)Cc2ccccc2)COC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 107.4 %

Procedure:
To 3-Dibenzylamino-oxetane-3-carbonitrile (156 mg) (prepared by Strecker synthesis in analogy to example 83/84, step a, from oxetan-3-one, dibenzyl-amine and trimethylsilyl cyanide) in methanol (10 ml) was added a catalytic amount of Raney nickel and the reaction mixture was then stirred at RT under an atmosphere of H2 for 8 h. The catalyst was removed by filtration, the filtrate concentrated under reduced pressure to provide the title compound (170 mg) as off-white solid, MS (ESI): 283.17 (MH+).
Reaction SMILES: [CH:1](=[O:6])[CH:2]=[C:3]([CH3:5])[CH3:4]>O>[CH2:1]([O:6][CH:1]([O:6][CH2:1][CH:2]=[C:3]([CH3:5])[CH3:4])[CH:2]=[C:3]([CH3:5])[CH3:4])[CH:2]=[C:3]([CH3:5])[CH3:4]
Reactant: CC(C)=CC=O
Solvent: O
Product: CC(C)=CCOC(C=C(C)C)OCC=C(C)C
Temperature: 100 °C
Yield: 281 %

Procedure:
In a 300-ml three-necked flask equipped with a water separator, 84 g (1 mole) of senecioaldehyde, 190 g (2.2 moles) of prenol and 2 mg of stannous chloride dihydrate were charged. The resulting mixture was heated at 100° C. under the pressure of 90 mmHg for 6 hours in an argon atmosphere while removing the water formed from the reaction mixture by azeotropic distillation. When water was no longer distilled, the solvent (hexane) and unreacted starting materials were distilled off under reduced pressure. Distillation of the residue under reduced pressure gave 223.3 g of senecioaldehyde diprenyl acetal (R1 =an isobutenyl group, R2 =a hydrogen atom and R3 =a prenyl group] (boiling point: 142° C./15 mmHg) (yield: 93.8%).
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]([C:7]2[C:8]3[N:16]=[N:15][N:14]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]5([O:29][Si](C)(C)C)[CH2:28][CH2:27][CH2:26][CH2:25]5)[N:19]=4)[C:9]=3[N:10]=[C:11]([NH2:13])[N:12]=2)[S:5][CH:6]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[CH3:1][C:2]1[N:3]=[C:4]([C:7]2[C:8]3[N:16]=[N:15][N:14]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]5([OH:29])[CH2:25][CH2:26][CH2:27][CH2:28]5)[N:19]=4)[C:9]=3[N:10]=[C:11]([NH2:13])[N:12]=2)[S:5][CH:6]=1
Reactant: Cc1csc(-c2nc(N)nc3c2nnn3Cc2cccc(C3(O[Si](C)(C)C)CCCC3)n2)n1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: Cc1csc(-c2nc(N)nc3c2nnn3Cc2cccc(C3(O)CCCC3)n2)n1
Yield: 23.4 %

Procedure:
A solution of 7-(4-methylthiazol-2-yl)-3-{6-[1-trimethylsilyloxy-1-cyclopentyl]pyridin-2-ylmethyl}-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-ylamine (0.105 g, 0.22 mmol) in THF (6 mL) was treated with tetrabutylammonium fluoride (1.0 M in THF, 0.33 mL, 0.33 mmol), refluxed for 90 min, cooled, concentrated in vacuo and partitioned between water and EtOAc. The aqueous phase was extracted with EtOAc and the combined organic phase dried (MgSO4), concentrated in vacuo, triturated with EtOAc and the resulting solid filtered to give the title compound (0.021 g, 24%) as a pale yellow solid.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][C:7]([O:8][C:9](Cl)=[O:10])=[CH:6][CH:5]=1)([O-:3])=[O:2].[Si:14]([O:21][CH2:22][CH2:23][CH2:24][OH:25])([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15].CN1CCOCC1>C(Cl)Cl>[Si:14]([O:21][CH2:22][CH2:23][CH2:24][O:25][C:9]([O:8][C:7]1[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:13][CH:12]=1)=[O:10])([C:17]([CH3:19])([CH3:20])[CH3:18])([CH3:16])[CH3:15]
Reactant: CC(C)(C)[Si](C)(C)OCCCO
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: CC(C)(C)[Si](C)(C)OCCCOC(=O)Oc1ccc([N+](=O)[O-])cc1
Reaction time: 2 h

Procedure:
A 0.604 g (3.00 mmol) sample of p-nitrophenoxycarbonylchloride in 3 mL of methylene chloride was added to a solution of 0.570 g (3.00 mmol) of 3-(t-butyldimethylsilyloxy)-1-propanol and 0.329 mL of 4-methylmorpholine in 2 mL of methylene chloride cooled in an ice bath. The solution was stirred for 2 hours. The mixture was diluted with methylene chloride, which was washed with water, dried and concentrated. The crude product was chromatographed on silica gel, eluting with 10% ethyl acetate in hexane. The solvent was removed and the product dried to afford 0.831 g of the title compound, which was taken directly to the next step.
Reaction SMILES: [CH2:1]([C@H:4]1[CH2:9][CH2:8][C@H:7]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21](Br)=[CH:20][CH:19]=3)=[CH:12][CH:11]=2)[CH2:6][CH2:5]1)[CH2:2][CH3:3].[Cu][C:26]#[N:27]>N1C=CC=CC=1.CN1CCCC1=O>[CH2:1]([C@H:4]1[CH2:9][CH2:8][C@H:7]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([C:26]#[N:27])=[CH:20][CH:19]=3)=[CH:12][CH:11]=2)[CH2:6][CH2:5]1)[CH2:2][CH3:3]
Reactant: CCC[C@H]1CC[C@H](c2ccc(CCc3ccc(Br)cc3)cc2)CC1
Reactant: N#C[Cu]
Solvent: c1ccncc1
Solvent: CN1CCCC1=O
Product: CCC[C@H]1CC[C@H](c2ccc(CCc3ccc(C#N)cc3)cc2)CC1

Procedure:
Analogously to Example 4(b), 1-[4-(trans-4-n-propylcyclohexyl)-phenyl]-2-(4-bromophenyl)-ethane is reacted with copper(I) cyanide in pyridine/N-methylpyrrolidone to give 1-[4-(trans-4-n-propylcyclohexyl)-phenyl]-2-(4-cyanophenyl)-ethane; m.p. 36°.
Reaction SMILES: [F:1][C:2]([F:32])([F:31])[C:3](C1C=CC(OCC)=CC=1)([OH:21])[CH2:4][O:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[C:9]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:8]=1.N1C=CC=CC=1.[C:39](OC(=O)C)(=[O:41])[CH3:40]>O>[F:32][C:2]([F:1])([F:31])[CH:3]([O:21][C:39](=[O:41])[CH3:40])[CH2:4][O:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([F:13])=[C:9]([O:14][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:8]=1
Reactant: CC(=O)OC(C)=O
Reactant: CCOc1ccc(C(O)(COCc2ccc(F)c(Oc3ccccc3)c2)C(F)(F)F)cc1
Solvent: c1ccncc1
Solvent: O
Product: CC(=O)OC(COCc1ccc(F)c(Oc2ccccc2)c1)C(F)(F)F
Reaction time: 8 h

Procedure:
1,1,1-Trifluoro-2-(4-ethoxyphenyl)-3-(3-phenoxy-4-fluorobenzyloxy)propan-2-ol (0.3 g), pyridine (1 cm3), acetic anhydride (10 cm3) and a catalytic amount of 4-N,N-dimethylaminopyridine (ca. 0.015 g) were mixed at the ambient temperature (ca. 22° C.), then heated at the reflux temperature for 6 hours. The mixture was allowed to stand overnight at the ambient temperature, and was then heated at reflux for a further 6 hours. Analysis by gas liquid chromatography showed 94% conversion to the product. Water was added and the product was extracted into diethyl ether (5×50 cm3). The combined ether layers were dried over anhydrous sodium sulphate and concentrated by evaporation under reduced pressure. The residual oil was purified by column chromatography on a silica gel support, eluted with n-hexane containing 12% by volume ethyl acetate, to give 1,1,1-trifluoro-2-acetoxy-3-(3-phenoxy-4-fluorobenzyloxy)propane (0.29 g) as a viscous oil.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][C:13]([O:19][CH2:20][CH2:21][CH2:22][C:23]([O:25]CC)=[O:24])=[CH:14][CH:15]=2)[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CO.C(O)C.[OH-].[Na+]>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:18][CH2:17][C:16]2[C:11](=[CH:12][C:13]([O:19][CH2:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])=[CH:14][CH:15]=2)[CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)CCCOc1ccc2c(c1)C[C@@H](NC(=O)OC(C)(C)C)CC2
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: CO
Product: CC(C)(C)OC(=O)N[C@H]1CCc2ccc(OCCCC(=O)O)cc2C1
Yield: 99.9 %

Procedure:
Ethyl (s)-4-[2-(tert-butoxycarbonylamino)-1,2,3,4-tetra-hydronaphthalen-7-yloxy]butyrate (988 mg) was dissolved in a mixed solvent of methanol (15 ml) and ethanol (15 ml), and 2N aqueous sodium hydroxide solution (3.0 ml) was added to the solution at room temperature with stirring. After reaction for 2 hours, the reaction mixture was concentrated in vacuo. To the resulting residue was added 10% aqueous citric acid solution, and the mixture was extracted with ethyl acetate. The extract was washed with brine and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to give (S)-4-[2-(tert-butoxycarbonylamino)-1,2,3,4-tetrahydronaphthalen-7-yloxy]butyric acid (914 mg) having a melting point of 150-153° C.
Reaction SMILES: [OH:1][B:2]1[C:6]2[CH:7]=[C:8]([O:13][CH3:14])[CH:9]=[C:10]([O:11][CH3:12])[C:5]=2[CH:4]([CH2:15][C:16]([O:18]CC)=[O:17])[O:3]1.[OH-].[Li+].Cl>CO>[OH:1][B:2]1[C:6]2[CH:7]=[C:8]([O:13][CH3:14])[CH:9]=[C:10]([O:11][CH3:12])[C:5]=2[CH:4]([CH2:15][C:16]([OH:18])=[O:17])[O:3]1
Reactant: CCOC(=O)CC1OB(O)c2cc(OC)cc(OC)c21
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Product: COc1cc(OC)c2c(c1)B(O)OC2CC(=O)O
Temperature: 25 °C
Reaction time: 3 h
Yield: 91.3 %

Procedure:
To a solution of ethyl 2-(1-hydroxy-4,6-dimethoxy-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate (0.28 g, 1.0 mmol) in methanol (5 mL) was added dropwise an aqueous solution of lithium hydroxide (2N, 2.5 mL) at 0° C. The reaction mixture was stirred at room temperature for 3 hr and acidified to pH=2 with diluted hydrochloride acid. The resulting mixture was extracted with ethyl acetate (2×20 mL), the combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel to give the title compound as a white solid (0.23 g, Yield: 92%). 1H NMR (400 Hz, CDCl3) δ 12.27 (s, 1H), 9.18 (s, 1H), 6.80-6.81 (d, J=2.0 Hz, 1H), 6.63-6.64 (d, J=4.0 Hz, 1H), 5.35-5.38 (m, 1H), 3.81 (s, 3H), 3.78 (s, 3H), 3.07-3.11 (m, 1H), 2.04-2.10 (m, 1H); MS (ESI) m/z=253 [M+H]+.
Reaction SMILES: S(Cl)([Cl:3])=O.O[CH2:6][C:7]1[N:8]=[CH:9][N:10]([S:15]([N:18]([CH3:20])[CH3:19])(=[O:17])=[O:16])[C:11]=1[CH2:12][CH2:13][CH3:14]>ClCCl>[Cl:3][CH2:6][C:7]1[N:8]=[CH:9][N:10]([S:15]([N:18]([CH3:20])[CH3:19])(=[O:17])=[O:16])[C:11]=1[CH2:12][CH2:13][CH3:14]
Reactant: CCCc1c(CO)ncn1S(=O)(=O)N(C)C
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: CCCc1c(CCl)ncn1S(=O)(=O)N(C)C

Procedure:
A solution of thionyl chloride (0.12 ml) in dry dichloromethane (1.2 ml) was added dropwise to a cold (0°) stirred solution of 4-(hydroxymethyl)-N,N-dimethyl-5-propyl-1H-imidazole-1-sulphonamide (340 mg) in dry dichloromethane (7.5 ml) under nitrogen. After 1.5 h the solution was washed with 8% sodium bicarbonate solution (2×15 ml) and the aqueous phase was extracted with dichloromethane (2×10 ml). The combined organic extracts were washed with water (15 ml), dried and evaporated to give the title compound (180 ml) as an oil, t.l.c. (ethyl acetate) Rf 0.68.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.C[O-].[Na+].Br[CH2:14][CH2:15][CH2:16][CH2:17][CH:18]=[CH2:19]>CO>[CH:14]([O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1)=[CH:15][CH2:16][CH2:17][CH2:18][CH3:19]
Reactant: O=Cc1ccc(O)cc1
Reactant: C=CCCCCBr
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: CCCCC=COc1ccc(C=O)cc1
Yield: 92.5 %

Procedure:
To a 500 ml egg-plant type flask, 4-hydroxybenzaldehyde (12.2 g, 100 mmol), a 28% solution of sodium methylate in methanol (18.5 ml, 130 mmol of sodium methylate), methanol (60 ml) and 6-bromo-1-hexene (20.0 ml, 150 mmol) were charged and heated under reflux for 18 hours. The reaction mixture was concentrated to about a half volume by evaporation of volatile components. Then, toluene (200 ml) and water (100 ml) were added to the concentrated mixture and shaken, followed by removal of an aqueous phase. An organic phase was washed with water (150 ml×3) and dried over anhydrous magnesium sulfate (10 g). After removing solids by filtration, volatile components were evaporated off from a filtrate to obtain 4-(1-hexenyloxy)benzaldehyde (18.9 g).