Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)([C:14]([NH2:16])=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N.[CH:26](OCC)(OCC)OCC>C(O)(=O)C.O>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]2([N:17]([C:18]3[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=3)[CH:26]=[N:16][C:14]2=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: NC(=O)C1(Nc2ccc(F)cc2)CCN(Cc2ccccc2)CC1
Reactant: CCOC(OCC)OCC
Agent: N
Solvent: O
Solvent: CC(=O)O
Product: O=C1N=CN(c2ccc(F)cc2)C12CCN(Cc1ccccc1)CC2
Reaction time: 0.17 h

Procedure:
A solution of 155 g (473 mmol) 1-benzyl-4-(4-fluoro-phenylamino)-piperidine-4-carboxylic acid amide in 200 ml triethyl orthoformate and 100 ml acetic acid was irradiated by microwaves in a sealed reactor to 150° C. for 10 min. and then to 200° C. for further 10 min. The reaction mixture was diluted with water, made alkaline with conc. ammonia, and extracted with dichloromethane. The combined organic extracts were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was crystallised from Et2O: 85 g 8-benzyl-1-(4-fluoro-phenyl)-1,3,8-triaza-spiro[4.5]dec-2-en-4-one: light brown crystals.
Reaction SMILES: C([O:3][C:4](=[O:31])[CH2:5][C:6]1[CH:7]=[N:8][N:9]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:14][C:13]=2[CH2:25][S:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH:10]=1)C.[OH-].[Li+]>CO.O>[C:27]([S:26][CH2:25][C:13]1[CH:14]=[C:15]([NH:18][C:19](=[O:24])[C:20]([CH3:23])([CH3:22])[CH3:21])[CH:16]=[CH:17][C:12]=1[CH2:11][N:9]1[CH:10]=[C:6]([CH2:5][C:4]([OH:31])=[O:3])[CH:7]=[N:8]1)([CH3:30])([CH3:29])[CH3:28]
Reactant: CCOC(=O)Cc1cnn(Cc2ccc(NC(=O)C(C)(C)C)cc2CSC(C)(C)C)c1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CC(C)(C)SCc1cc(NC(=O)C(C)(C)C)ccc1Cn1cc(CC(=O)O)cn1

Procedure:
{1-[2-tert-Butylsulfanylmethyl-4-(2,2-dimethyl-propionylamino)-benzyl]-1H-pyrazol-4-yl}-acetic acid ethyl ester (0.038 g, 0.09 mmol) in MeOH and H2O was hydrolyzed with lithium hydroxide to give the title compound.
Reaction SMILES: [OH:1][C:2]1[CH:14]=[CH:13][CH:12]=[C:11]([OH:15])[C:3]=1[C:4]([O:6][CH2:7][CH2:8][S:9][CH3:10])=[O:5].[H-].[Na+].Cl[C:19]1[N:24]=[C:23]([O:25][CH3:26])[CH:22]=[C:21]([O:27][CH3:28])[N:20]=1>CN(C=O)C>[CH3:28][O:27][C:21]1[CH:22]=[C:23]([O:25][CH3:26])[N:24]=[C:19]([O:1][C:2]2[CH:14]=[CH:13][CH:12]=[C:11]([O:15][C:19]3[N:24]=[C:23]([O:25][CH3:26])[CH:22]=[C:21]([O:27][CH3:28])[N:20]=3)[C:3]=2[C:4]([O:6][CH2:7][CH2:8][S:9][CH3:10])=[O:5])[N:20]=1
Reactant: CSCCOC(=O)c1c(O)cccc1O
Reactant: COc1cc(OC)nc(Cl)n1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1cc(OC)nc(Oc2cccc(Oc3nc(OC)cc(OC)n3)c2C(=O)OCCSC)n1
Temperature: 0 °C

Procedure:
Methylthioethyl 2,6-dihydroxybenzoate (4.5 g) was dissolved in DMF, and 60% sodium hydride (1.6 g) was added thereto. Then, 2-chloro-4,6-dimethoxypyrimidine (3.5 g) was added thereto, and the mixture was heated and reacted at a temperature within a range of from 90 to 110° C. for two hours. The reaction solution was poured into ice water and then extracted twice with ethyl acetate. The ethyl acetate layer was washed with water and dried over anhydrous sodium sulfate. After removing inorganic substances by filtration, the solvent was distilled off under reduced pressure. The residue was purified by column chromatography to obtain the above identified compound as a colorless viscous liquid. (η20D: 1.5706).
Reaction SMILES: S([O-])(OC(C)(C)S(OC1C=CC(O)=CC=1)(=O)=O)(=O)=O.[C:20]([OH:43])(=O)[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=[CH:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41].C1(N=C=NC2CCCCC2)CCCCC1.[NH2:59][C@@H:60]([C:62]([OH:64])=[O:63])[CH3:61].C(N(CC)CC)C>C(#N)C.O>[C:20]([NH:59][C@@H:60]([C:62]([OH:64])=[O:63])[CH3:61])(=[O:43])[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=[CH:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41]
Reactant: CCCCCCCCCC=CC=CC=CC=CC=CC=CC(=O)O
Reactant: C[C@@H](N)C(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CC(C)(OS(=O)(=O)[O-])S(=O)(=O)Oc1ccc(O)cc1
Solvent: O
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCCCCCCCCC=CC=CC=CC=CC=CC=CC(=O)N[C@H](C)C(=O)O
Temperature: 0 °C
Reaction time: 2 h
Yield: 40 %

Procedure:
4-hydroxyphenyldimethylsulfomethyl sulfate 2.66 g (0.01 mol) was heated and dissolved in 40 ml of acetonitrile. Docosahexaenoic acid 3.28 g (0.01 mol) was added to the solution obtained in a stream of nitrogen, and the mixture was stirred at 0° C. To the mixture solution, dicyclohexyl carbodiimide 2.06 g (0.01 mol) was added little by little, and the solution was stirred for 2 hours at 0° C. and then for 2 hours at room temperature. The solution reacted was filtered to remove dicyclohexyl urea, and the filtrate was distilled in vacuo to obtain oily residue. D-alanine 0.89 g (0.01 mol) and triethyl amine 1.4 ml (0.01 mol) were added to 10 ml of water. An acetonitrile solution of the above oily residue was added to the mixture with stirring, and stirred for 10 hours at room temperature. After reaction, the reaction mixture was concentrated under reduced pressure. The concentrate was adjusted to pH 2 or 3 with 6N-HCl, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried over anhydrous sodium acetate, and freed of solvent in vacuo. The oily residue obtained was purified by column chromatography (column: 2.5×15 cm) on 50 g of silica gel and N-docosahexaenoyl-D-alanine 1.6 g was obtained.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:19])[CH2:4][NH:5][C:6](=C=S)[CH2:7][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH3:9].[BH4-].[Na+]>C1COCC1.CO>[CH3:1][O:2][C:3](=[O:19])[CH2:4][NH:5][CH2:6][CH2:7][N:8]([C:10]([O:12][C:13]([CH3:15])([CH3:14])[CH3:16])=[O:11])[CH3:9]
Reactant: COC(=O)CNC(=C=S)CN(C)C(=O)OC(C)(C)C
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: COC(=O)CNCCN(C)C(=O)OC(C)(C)C

Procedure:
To a suspension of the N-[(N-Boc)(N-methyl)(1-thiocarbonyl)-2-aminoethyl]-glycine methyl ester (2.67 g, 0.0097 mol) and NiCl26H2O (18.39 g, 0.077 mol) in THF:MeOH 1:1 (100 ml) at −20° C., NaBH4 (8.78 g, 0.23 mol) was slowly added so that the temperature did not exceed 0° C. After addition of the NaBH4, the reaction was allowed to go to room temperature. The reaction mixture was filtered several times through celite and evaporated to dryness. The product was isolated by column chromatography on silica gel with CH2CL2/MeOH 90:10 eluent. The yield of the title compound was 60%.
Reaction SMILES: C[Si]([N-:5][Si](C)(C)C)(C)C.[Li+].C1COCC1.[C:16]([C:18]1[CH:45]=[CH:44][C:21]([C:22]([NH:24][C:25]2[CH:30]=[C:29]([C:31]3[S:32][CH:33]=[CH:34][CH:35]=3)[CH:28]=[CH:27][C:26]=2[NH:36][C:37](=[O:43])[O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:23])=[CH:20][N:19]=1)#[N:17].Cl>>[C:16]([C:18]1[CH:45]=[CH:44][C:21]([C:22]([NH:24][C:25]2[CH:30]=[C:29]([C:31]3[S:32][CH:33]=[CH:34][CH:35]=3)[CH:28]=[CH:27][C:26]=2[NH:36][C:37](=[O:43])[O:38][C:39]([CH3:41])([CH3:42])[CH3:40])=[O:23])=[CH:20][N:19]=1)(=[NH:5])[NH2:17]
Reactant: CC(C)(C)OC(=O)Nc1ccc(-c2cccs2)cc1NC(=O)c1ccc(C#N)nc1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Agent: Cl
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)Nc1ccc(-c2cccs2)cc1NC(=O)c1ccc(C(=N)N)nc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 48 %

Procedure:
To a 1M solution of lithium bis(trimethylsilyl)amide in THF (0.0.76 mL, 0.76 mmol) at 0° C. was added compound 251 (0.10 g, 0.24 mmol). The reaction mixture was allowed to warm to room temperature, stirred for 18 h, cooled to 0° C., treated with 1N HCl (15 mL), stirred for 30 min and concentrated. The residue was diluted with AcOEt and extracted with H2O. The aqueous phase was collected, neutralized with 1N NaOH, extracted with AcOEt, dried over MgSO4, filtered and concentrated. The resulting brown solid was triturated with diethyl ether to give intermediate 252 (50 mg, 48% yield).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([Br:8])[CH:5]=[C:4]([Br:9])[C:3]=1[OH:10].[N:11]#[C:12]Br>>[Br:1][C:2]1[CH:7]=[C:6]([Br:8])[CH:5]=[C:4]([Br:9])[C:3]=1[O:10][C:12]#[N:11]
Reactant: N#CBr
Reactant: Oc1c(Br)cc(Br)cc1Br
Product: N#COc1c(Br)cc(Br)cc1Br
Yield: 60 %

Procedure:
Analogous to Example 1, 2,4,6-tribromophenol was reacted with cyanogen bromide to obtain the title compound as white crystals. The yield was 60% of theory. The product was identified by elementary analysis and its NMR spectrum as well as by the absorption of the cyanato group at 2270 cm-1 in the IR spectrum.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH:11]([C:17]2[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=2[F:24])[CH:12]([CH3:16])[CH2:13][CH2:14]O)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH3:25][S:26]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])(=[O:28])=[O:27].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C([O-])=O)=NC([O-])=O>O1CCCC1.C(OCC)(=O)C.CCCCCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([CH:11]([C:17]2[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:18]=2[F:24])[CH:12]([CH3:16])[CH2:13][CH2:14][N:29]([S:26]([CH3:25])(=[O:28])=[O:27])[C:30](=[O:36])[O:31][C:32]([CH3:33])([CH3:35])[CH3:34])(=[O:10])=[O:9])=[CH:6][CH:7]=1
Reactant: CC(CCO)C(c1cc(F)ccc1F)S(=O)(=O)c1ccc(Cl)cc1
Reactant: CC(C)(C)OC(=O)NS(C)(=O)=O
Agent: O=C([O-])N=NC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(CCN(C(=O)OC(C)(C)C)S(C)(=O)=O)C(c1cc(F)ccc1F)S(=O)(=O)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 95 %

Procedure:
The 4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)-3-methyl-1-butanol (97.2 mg, 0.259 mmol) obtained in Example 239, t-butyl N-methylsulfonylcarbamate (101 mg, 0.518 mmol) and triphenylphosphine (138 mg, 0.518 mmol) were dissolved in tetrahydrofuran (3 ml), followed by the addition of diisoopropyl azodicarboxylate (102 μl, 0.518 mmol) at room temperature. The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with ethyl acetate, washed with a saturated aqueous solution of ammonium chloride, water and brine, dried over magnesium sulfate and then concenetrated. The residue thus obtained was subjected to flash chromatography on a silica gel column, and the fraction obtained from the hexane:ethyl acetate=3:2 eluate was concentrated, whereby the title compound (136 mg, 0.246 mmol, 95%) was obtained as a colorless amorphous substance.
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([F:9])=[CH:4][C:3]=1[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12].[CH2:16]([O:18][C:19](=O)[O:20]CC)[CH3:17].[H-].[Na+]>C1(C)C=CC=CC=1>[CH2:14]([O:13][C:11](=[O:12])[CH:10]([C:3]1[CH:4]=[C:5]([F:9])[CH:6]=[C:7]([F:8])[C:2]=1[F:1])[C:19]([O:18][CH2:16][CH3:17])=[O:20])[CH3:15]
Reactant: CCOC(=O)Cc1cc(F)cc(F)c1F
Reactant: CCOC(=O)OCC
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CCOC(=O)C(C(=O)OCC)c1cc(F)cc(F)c1F
Temperature: 0 °C
Yield: 82.9 %

Procedure:
Ethyl 2-(2,3,5-trifluorophenyl)-acetate (29 g) was slowly added to a mixture of diethylcarbonate (63 g) and sodium hydride (9.5 g) in toluene (350 ml). After being refluxed for 3 hours, the reaction mixture was cooled, treated with ice-water and washed with water. The organic layer was separated, dried and filtered. The filtrate was concentrated in vacuo to yield 32 g of the title compound.
Reaction SMILES: [CH3:1][Li].[OH:3][C:4]1[CH:13]=[C:12]2[C:7]([CH:8]([C:15]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=4)[CH:18]=[CH:17][CH:16]=3)[CH2:9]C(=O)[O:11]2)=[CH:6][CH:5]=1.CC[O:27][CH2:28][CH3:29]>>[OH:11][C:12]1[CH:13]=[C:4]([OH:3])[CH:5]=[CH:6][C:7]=1[CH:8]([C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:18]=[CH:17][CH:16]=1)[CH2:9][C:28]([CH3:29])([OH:27])[CH3:1]
Reactant: O=C1CC(c2cccc3ccccc23)c2ccc(O)cc2O1
Reactant: [Li]C
Reactant: CCOCC
Product: CC(C)(O)CC(c1ccc(O)cc1O)c1cccc2ccccc12

Procedure:
To a stirred solution of methyl lithium in ether (80 ml, 1.9M solution) at ambient temperature under nitrogen was added portionwise over 0.5 hour finely divided 3,4-dihydro-7-hydroxy-4-(1-naphthyl)coumarin (7.52 g). The ether boiled during the addition and the solid material gradually dissolved. After the addition was complete the solution was boiled under reflux for 4 hours then cooled and poured into acid. The ether extract yielded 4-(2,4-dihydroxyphenyl)-2-methyl-4-(1-naphthyl)-2-butanol which was dissolved in glacial acetic acid (55 ml) and boiled under reflux overnight. The product was poured into water (200 ml) and extracted into ether. The ether extract was washed with water and aqueous sodium bicarbonate then dried (magnesium sulphate). Removal of the solvent gave the title compound (7.70 g) as a foam containing some ether.
Reaction SMILES: [C:1]1(=[O:10])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[CH:11]([C:13]1[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=1)=O.N1CCCCC1>C(O)(=O)C>[O:10]=[C:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=[CH:11][C:13]1[CH:22]=[CH:21][C:16]([C:17]([O:19][CH3:20])=[O:18])=[CH:15][CH:14]=1
Reactant: O=C1CCc2ccccc21
Reactant: COC(=O)c1ccc(C=O)cc1
Solvent: CC(=O)O
Solvent: C1CCNCC1
Product: COC(=O)c1ccc(C=C2Cc3ccccc3C2=O)cc1

Procedure:
A mixture of indan-1-one (3.3 g), methyl 4-formylbenzoate (5.0 g), piperidine (0.6 ml) and glacial acetic acid (0.5 ml) was heated on a steam bath for 3 hours. The solid mass obtained was boiled up in industrial methylated spirits (200 ml) and then hot filtered. The solid residue obtained was washed with industrial methylated spirits and dried to give methyl 4-(1-oxoindan-2-ylidenemethyl)benzoate, m.p. 194-198° C.
Reaction SMILES: [C:1]1([Mg]Br)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O1CCCC1.[C:14]([O:18][C:19]([N:21]1[CH2:27][C@H:26]([O:28][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])[CH2:25][C@H:22]1[CH:23]=[O:24])=[O:20])([CH3:17])([CH3:16])[CH3:15].O>O1CCCC1>[C:14]([O:18][C:19]([N:21]1[CH2:27][C@H:26]([O:28][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])[CH2:25][C@H:22]1[CH:23]([OH:24])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:20])([CH3:17])([CH3:16])[CH3:15]
Reactant: Br[Mg]c1ccccc1
Reactant: CC(C)(C)OC(=O)N1C[C@H](O[Si](C)(C)C(C)(C)C)C[C@H]1C=O
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)N1C[C@H](O[Si](C)(C)C(C)(C)C)C[C@H]1C(O)c1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 96.8 %

Procedure:
2.0M Phenylmagnesium bromide-tetrahydrofuran solution (22.8 ml, 45.6 mmol) was added dropwise to a solution of (2S,4R)-N-t-butoxycarbonyl-4-(t-butyldimethylsiloxy)prolinal (10 g, 30.4 mmol) in tetrahydrofuran (200 ml) at -78° C. in a nitrogen stream over 15 minutes. This reaction solution was gradually warmed and stirred at room temperature for 3 hours. After addition of water, the reaction solution was concentrated in vacuo. The resulting residue was poured into a liquid mixture of ethyl acetate with water. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated in vacuo. The resulting oily residue was subjected to silica gel column chromatography (Wakogel™ C-300, heptane-ethyl acetate=4:1) to give (2S,4R)-N-t-butoxycarbonyl-4-t-butyldimethylsiloxy-2-(α-hydroxybenzyl)pyrrolidine (12.0 g, yield: 96.8%) as a colorless oily substance.
Reaction SMILES: [Cl-].[Br:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][N:7]([C:17](=[O:20])[CH2:18][NH3+:19])[CH:8]2[CH2:13][C:14](O)=[O:15].BrC1C=CC=C2C=1CCN(C(=O)CNC(OC(C)(C)C)=O)C2CC(O)=O>O1CCOCC1.Cl>[Br:2][C:3]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][CH2:6][N:7]1[C:17](=[O:20])[CH2:18][NH:19][C:14](=[O:15])[CH:13]=[C:8]12
Reactant: [NH3+]CC(=O)N1CCc2c(Br)cccc2C1CC(=O)O
Agent: CC(C)(C)OC(=O)NCC(=O)N1CCc2c(Br)cccc2C1CC(=O)O
Agent: Cl
Agent: [Cl-]
Solvent: C1COCCO1
Product: O=C1C=C2c3cccc(Br)c3CCN2C(=O)CN1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
2-(5-bromo-1-(carboxymethyl)-3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethanaminium chloride. To a stirred solution of 2-(5-bromo-2-(2-((tert-butoxycarbonyl)amino)acetyl)-1,2,3,4-tetrahydroisoquinolin-1-yl)acetic acid (110 g, 257 mmol) in dioxane (1290 mL), 4N HCl in dioxane (644 mL, 2574 mmol) was added and the reaction mixture was stirred at RT for 24 h. The white precipitate was filtered off and the white solid was washed with a small amount of diethyl ether (2×). The HCl salt was dried under high vacuo overnight to yield the title compound as white solid (88 g). UPLC-MS: MS 327.1/329.1 (M+H+); UPLC rt 0.56 min.
Reaction SMILES: [Li+].CC([N-]C(C)C)C.COP(O)([O:13][CH3:14])=O.[CH3:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27]C=[CH:25][CH:24]=2)=[CH:19][CH:18]=1>C1COCC1>[CH3:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:24]=[CH:25][C:14]([OH:13])=[CH:27][CH:28]=2)=[CH:19][CH:18]=1
Reactant: COP(=O)(O)OC
Reactant: Cc1ccc(-c2ccccc2)cc1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: Cc1ccc(-c2ccc(O)cc2)cc1
Temperature: -78 °C
Reaction time: 1 h
Yield: 33.8 %

Procedure:
To a solution of LDA [prepared from diisopropylamine (3.5 mL, 24.5 mmol) and 2.2M n-butyllithium in hexanes (12 mL, 26.4 mmol)] in THF (120 mL) at −78° C. was added a solution of 4′-methyl-biphenyl dimethyl phosphate (6.1 g, 20.9 mmol) in THF (20 mL). The mixture was stirred at −78° C. for 1 h and then at r.t. for 1 h. After quenching with 2M aqueous HOAc (10 mL), solvent was removed in vacuo. The residue was diluted with H2O and extracted with EtOAc. The EtOAc extract was washed with H2O (2×), dried (MgSO4) and concentrated. Chromatography over silica gel and elution with hexanes:EtOAc (3:2) provided 1.3 g of 4′-methyl-4-hydroxybiphenyl. Further elution gave 4.0 g (65.5%) of the title compound as a white solid.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:11]([OH:13])=O)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C(=O)CCC1=O.C1CCC(N=C=NC2CCCCC2)CC1.[NH:37]1[CH2:43][CH2:42][CH2:41][C@H:38]1[CH2:39][OH:40]>C1COCC1>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:11]([N:37]1[CH2:43][CH2:42][CH2:41][C@H:38]1[CH:39]=[O:40])=[O:13])[CH3:10])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: OC[C@@H]1CCCN1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: O=C1CCC(=O)N1O
Solvent: C1CCOC1
Product: C[C@H](NC(=O)OC(C)(C)C)C(=O)N1CCC[C@H]1C=O
Temperature: 4 °C
Reaction time: 21 h

Procedure:
In 200 ml of THF was dissolved 22.1 g of t-butyloxycarbonylalanine. To this solution were added under cooling with edible salt and ice 11.5 g of HOSu and 20.6 g of DCC, and the mixture was stirred for 21 hours at 4° C. The reaction liquid was filtered and the filtrate was evaporated whereby a semi-solid substance was obtained. This substance was recrystallized from chloroform to obtain a white solid substance which was then dissolved in 400 ml of THF. To this solution was added 7.5 g of L-prolinol, and the mixture was stirred for 72 hours at room temperature. After removal of THF by distillation, the residue was dissolved in 300 ml of ethyl acetate and the solution was washed with 100 ml of 1-M Na2CO3, dehydrated with anhydrous Na2SO4 and evaporated until dryness. To the resultant oily substance were added 32.5 g of WSCD.HCl and 130 ml of redistilled DMSO, and the mixture was stirred for 10 minutes. Subsequently, 6 ml of DMSO solution of 2-M anhydrous H3PO4 was added and the mixture was stirred for further 2 hours. The reaction was stopped with 300 ml of a buffer solution of 1-M potassium phosphate of pH 7.5. The reaction mixture was extracted with 250 ml of ethyl acetate, and the extract was dried over anhydrous Na2SO4. The ethyl acetate was distilled off and the residue was dissolved in 250 ml of ethanol. To this solution was added 200 g of NaHSO3 in 350 ml of water, and the mixture was stirred vigorously for 10 minutes. After concentration of the ethanol up to about 350 ml, unreacted materials were eliminated twice with 100 ml of ether, and solid Na2CO3 was added until the pH value of the liquid became 9. After 5 minutes, the reaction liquid was extracted twice with 100 ml of ether, and the ether was then distilled off to leave an oily substance. Yield 1.2 g (4.5%).
Reaction SMILES: C1(S[C:8]2[S:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)C=CC=CC=1.[C:17]([C:19]1[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[CH:22]=[CH:21][C:20]=1[CH3:28])#[N:18].[CH:29](N(C(C)C)CC)(C)[CH3:30]>C(#N)C>[C:17]([C:19]1[CH:24]=[C:23]([N+:25]([O-:27])=[O:26])[CH:22]=[CH:21][C:20]=1[CH:28]=[C:8]1[N:12]([CH2:29][CH3:30])[C:11]2[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=2[S:9]1)#[N:18]
Reactant: Cc1ccc([N+](=O)[O-])cc1C#N
Reactant: c1ccc(Sc2nc3ccccc3s2)cc1
Reactant: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: CCN1C(=Cc2ccc([N+](=O)[O-])cc2C#N)Sc2ccccc21

Procedure:
2-Phenylthiobenzothiazole ethiodide (3.99 g., 0.01 mole) and 2.00 g. (0.012 mole) of 2-cyano-4-nitrotoluene were dissolved in 25 ml. of acetonitrile and then 2.58 g. (0.02 mole) of diisopropyl ethylamine was added. The reaction mixture was refluxed two hours and then cooled for several hours. The green iridescent crystalline product was collected and washed with a small amount of acetonitrile. After drying 1.13 g. of product, m.p. 237°-9° (dec.) was obtained.
Reaction SMILES: C([CH:3]1[C:11]2[C:6](=[CH:7][C:8]3OCO[C:9]=3[CH:10]=2)[C:5](=[O:15])[CH2:4]1)C.CC1C2C(=C(OC)C=CC=2C)C(=O)C1>C(O)C>[C:5]1(=[O:15])[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH2:3][CH2:4]1
Reactant: CCC1CC(=O)c2cc3c(cc21)OCO3
Agent: COc1ccc(C)c2c1C(=O)CC2C
Solvent: CCO
Product: O=C1CCc2ccccc21

Procedure:
The above-described aromataic composition of the present process is added in an amount of 1 ppm to the material flour of cakes, and this flour is baked to make cakes. Likewise, a 5 % ethanol solution of the mixture (in the ratio 10:7) of 3-ethyl-5,6-methylenedioxyindan-1-one and 3,4-dimethyl-7-methoxyindan-1-one is added to the material flour but in an amount to give 10 ppm by weight of said indanone compounds mixture thereto, and this material is baked.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][N:8]([Si](C(C)C)(C(C)C)C(C)C)[C:5]2=[N:6][CH:7]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[Cl:1][C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1
Reactant: CC(C)[Si](C(C)C)(C(C)C)n1ccc2cc(Cl)cnc21
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: Clc1cnc2[nH]ccc2c1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To 5-chloro-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (79, 1.40 g, 4.53 mmol) in tetrahydrofuran (15 mL) was added tetra-n-butylammonium fluoride (1.42 g, 5.43 mmol). The reaction mixture was stirred at room temperature for 10 minutes. The reaction mixture was concentrated and isolated by silica gel column chromatography eluting with 30% ethyl acetate in hexane to give the compound (80, 0.40 g. 58% over 2 steps). MS (ESI)[M−H+]−=153.1.
Reaction SMILES: [CH2:1](Cl)[CH2:2][OH:3].[OH:5][C:6]1[C:11]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:10][C:9]([CH2:19][CH3:20])=[C:8]([CH2:21][CH3:22])[N:7]=1.[OH-].[Na+]>C(O)(C)(C)C>[OH:3][CH2:2][CH2:1][N:7]1[C:8]([CH2:21][CH3:22])=[C:9]([CH2:19][CH3:20])[N:10]=[C:11]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:6]1=[O:5]
Reactant: CCc1nc(O)c(Cc2ccccc2)nc1CC
Reactant: OCCCl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)(C)O
Product: CCc1nc(Cc2ccccc2)c(=O)n(CCO)c1CC
Temperature: 60 °C
Reaction time: 3 h
Yield: 86.1 %

Procedure:
Ethylene chlorohydrin (20.15 g, 0.25M) was added to a solution of 2-hydroxy-3-benzyl-5,6-diethyl-pyrazine (12.10 g, 50 mM) and 5N NaOH (50 ml) in t-butanol (150 ml), and stirred at 60° C. for 3 hours. The t-butanol was distilled off in vacuo, water was added thereto and the mixture was extracted three times with chloroform. The extract was dried with anhydrous magnesium sulfate and concentrated in vacuo. The residue was charged on a column of silica-gel (C-200, 230 g) packed with chloroform and eluted with chloroform-methanol (100:1) to obtain compound 640 (12.31 g, yield: 58.7%).