Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([S:8][CH3:9])[N:3]=1.C(N(CC)CC)C.[CH3:17][Si:18]([C:21]#[CH:22])([CH3:20])[CH3:19].CCCCCC>O1CCCC1.[Cu]I>[CH3:9][S:8][C:4]1[N:3]=[C:2]([C:22]#[C:21][Si:18]([CH3:20])([CH3:19])[CH3:17])[CH:7]=[CH:6][N:5]=1
Reactant: C#C[Si](C)(C)C
Reactant: CSc1nccc(I)n1
Agent: [Cu]I
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: CCCCCC
Product: CSc1nccc(C#C[Si](C)(C)C)n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 97.7 %

Procedure:
4-Iodo-2-(methylsulfanyl)pyrimidine (2.0 g, 8.1 mmol) was dissolved in anhydrous tetrahydrofuran (50 mL). To this solution was added triethylamine (1.4 mL, 10.1 mmol), copper (I) iodide (80 mg, 0.4 mmol) and dichlorobis(triphenylphosphine) palladium (II) (140 mg, 0.24 mmol). (Trimethylsilyl)acetylene (1.4 mL, 10.1 mmol) was added dropwise to the resulting solution. After the addition of (trimethylsilyl)acetylene was complete the reaction was stirred at room temperature for 2 hours. Hexane was added to the reaction mixture and the mixture was filtered to remove precipitates. The solution was concentrated to give a syrup, that was purified by silica gel chromatography (1:1 ethyl acetate:hexane) to give 1.76 g (99%) of 2-(methylsulfanyl)-4-[(trimethylsilyl)ethynyl]pyrimidine. 2-(Methylsulfanyl)-4-[(trimethylsilyl)ethynyl]pyrimidine (1.76 g, 8.0 mmol) was dissolved in methanol (60 mL). To this solution was added potassium fluoride (467 mg, 8.0 mmol) and the resulting mixture stirred at room temperature for 5 minutes. The solution was concentrated and ethyl acetate and water were added. The phases were separated and the aqueous phase extracted with additional ethyl acetate. The organics were combined, dried over magnesium sulfate, filtered and concentrated to give 1.0 g (83%) of 4-ethynyl-2-(methylsulfanyl)pyrimidine as a white solid. 1H NMR (CDCl3): δ 8.51 (d, 1H), 7.06 (d, 1H), 3.34 (s, 1H), 2.56 (s, 3H); MS m/z 151 (M+1).
Reaction SMILES: [I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[CH:9]([C@@H:11]1[CH2:16][C@H:15]([N:17]([C:22]([C:24]2[N:28]([CH2:29][CH2:30][CH2:31][CH2:32][O:33][CH3:34])[C:27]3[CH:35]=[CH:36][CH:37]=[CH:38][C:26]=3[N:25]=2)=[O:23])[CH2:18][CH:19]([CH3:21])[CH3:20])[CH2:14][N:13]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:12]1)=[O:10].[Cl-].[NH4+]>CS(C)=O>[CH3:34][O:33][CH2:32][CH2:31][CH2:30][CH2:29][N:28]1[C:27]2[CH:35]=[CH:36][CH:37]=[CH:38][C:26]=2[N:25]=[C:24]1[C:22]([N:17]([CH2:18][CH:19]([CH3:20])[CH3:21])[C@H:15]1[CH2:16][C@@H:11]([CH:9]2[CH2:2][O:10]2)[CH2:12][N:13]([C:39]([O:41][C:42]([CH3:43])([CH3:45])[CH3:44])=[O:40])[CH2:14]1)=[O:23]
Reactant: C[S+](C)(C)=O
Reactant: COCCCCn1c(C(=O)N(CC(C)C)[C@H]2C[C@@H](C=O)CN(C(=O)OC(C)(C)C)C2)nc2ccccc21
Agent: [Cl-]
Agent: [H-]
Agent: [I-]
Solvent: CS(C)=O
Product: COCCCCn1c(C(=O)N(CC(C)C)[C@H]2C[C@@H](C3CO3)CN(C(=O)OC(C)(C)C)C2)nc2ccccc21
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 49.8 %

Procedure:
Trimethylsulfoxonium iodide (240 mg) was dissolved in DMSO (5 ml), sodium hydride (60% in oil, 45 mg) was added, and the mixture was stirred at room temperature for 30 min. A solution of tert-butyl (3R,5S)-3-formyl-5-[{[1-(4-methoxybutyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]piperidine-1-carboxylate (450 mg) in DMSO (10 ml) was added and the mixture was stirred at room temperature for 30 min. The reaction mixture was poured into saturated aqueous ammonium chloride solution and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure. The residue was subjected to silica gel column chromatography, and a fraction eluted with ethyl acetate was concentrated under reduced pressure to give the object product (230 mg).
Reaction SMILES: [C:1]([C:4]1[C:5]([CH3:18])=[C:6]2[C:11](=[C:12]([CH3:14])[CH:13]=1)S[CH2:9][C:8]([CH3:16])([CH3:15])[C:7]2=[O:17])(=[O:3])[CH3:2].C(O)(=O)C.OO.[S:25]([O-:28])(O)=[O:26].[Na+]>O>[C:1]([C:4]1[C:5]([CH3:18])=[C:6]2[C:11](=[C:12]([CH3:14])[CH:13]=1)[S:25](=[O:28])(=[O:26])[CH2:16][C:8]([CH3:15])([CH3:9])[C:7]2=[O:17])(=[O:3])[CH3:2]
Reactant: CC(=O)c1cc(C)c2c(c1C)C(=O)C(C)(C)CS2
Reactant: O=S([O-])O
Agent: OO
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: CC(=O)c1cc(C)c2c(c1C)C(=O)C(C)(C)CS2(=O)=O
Yield: 97 %

Procedure:
A 100-ml round-bottomed flask was charged with 1.18 g (4.50 mmol) of 6-acetyl-3,3,5,8-tetramethylthiochroman-4-one, 2 ml of acetic acid and 1.12 g (9.88 mmol) of a 30 wt % hydrogen peroxide aqueous solution, and the mixture was allowed to react at 80° C. for 2 and half hours. The reaction mixture was diluted with about 30 ml of water, and a sodium hydrogensulfite aqueous solution was added to decompose excess peroxide. Then, the mixture was extracted with ethyl acetate. An organic layer was washed with a saturated sodium hydrogencarbonate aqueous solution and with a saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to give 1.28 g (yield 97%) of 6-acetyl-3,3,5,8-tetramethylthiochroman-4-one-1,1-dioxide.
Reaction SMILES: [CH:1]([OH:3])=O.C(OC(=O)C)(=O)C.Cl.[CH3:12][C:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]2[CH2:22][CH2:23][CH2:24][CH:25]([NH2:26])[C:14]=12.O>O1CCCC1>[CH3:12][C:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]2[CH2:22][CH2:23][CH2:24][CH:25]([NH:26][CH:1]=[O:3])[C:14]=12
Reactant: O=CO
Reactant: Cc1c2n(c3ccccc13)CCCC2N
Agent: Cl
Solvent: CC(=O)OC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: Cc1c2n(c3ccccc13)CCCC2NC=O
Temperature: 60 °C
Reaction time: 2 h
Yield: 99 %

Procedure:
A mixture of formic acid (6 mL) and acetic anhydride (12 mL) was heated at 60° C. for 4 hours. A solution of 6,7,8,9-tetrahydro-10-methylpyrido[1,2-a]indol-9-amine hydrochloride (7.5 g, 37.5 mmol), in dry tetrahydrofuran (60 mL) was added upon cooling to the resultant mixed anhydride. The reaction mixture was stirred at 25° C. for 2 hours, poured into water (150 mL) and extracted with ether (3×100 mL). The combined extracts were washed successively with 5% hydrochloric acid, 5% sodium bicarbonate, and water. The ethereal solution was dried over MgSO4, filtered, and evaporated. The solid residue was crystallized from benzene/hexane to give 8.5 g (99%) of the title formamide as a yellow solid, m.p. 133°-5° C. Analytical sample melted at 136° C.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([CH:12]=1)=[CH:10][C:9]([O:13][CH:14]([S:18][CH3:19])[C:15]([OH:17])=O)=[CH:8][CH:7]=2)#[CH:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH2:42][C:43]1([CH2:47][OH:48])[CH2:46][CH2:45][CH2:44]1.[NH4+].[Cl-]>CC#N.CCN(CC)CC>[C:1]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([CH:12]=1)=[CH:10][C:9]([O:13][CH:14]([S:18][CH3:19])[C:15]([NH:42][C:43]1([CH2:47][OH:48])[CH2:46][CH2:45][CH2:44]1)=[O:17])=[CH:8][CH:7]=2)#[CH:2]
Reactant: NC1(CO)CCC1
Reactant: C#Cc1cnc2ccc(OC(SC)C(=O)O)cc2c1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: [Cl-]
Solvent: CCN(CC)CC
Solvent: CC#N
Product: C#Cc1cnc2ccc(OC(SC)C(=O)NC3(CO)CCC3)cc2c1
Reaction time: 1 h
Yield: 331.1 %

Procedure:
To a solution of (3-ethynyl-quinolin-6-yloxy)-methylsulfanyl-acetic acid (1.10 g) in CH3CN (40 ml) was added Et3N (2.25 ml), AHOBT (0.06 g), TBTU (1.50 g) and (1-amino-cyclobutyl)-methanol (0.06 g) at room temperature, under nitrogen atmosphere. The mixture was stirred at the same temperature during 1 hour, then poured into sat aq NH4Cl and extracted with ethyl acetate (2×20 ml). The organic phase was separated and washed with aq Na2S2O3 and sat. aq. NaCl then dried over anhydrous sodium sulphate, filtered and evaporated under vacuum. Purification by flash chromatography (ethyl acetate/cyclohexane, 2/1) gave 2-(3-ethynyl-quinolin-6-yloxy)-N-(1-hydroxymethyl-cyclobutyl)-2-methylsulfanyl-acetamide (0.70 g) as a yellow oil.
Reaction SMILES: [Si]([O:8][CH:9]1[CH2:14][CH2:13][C:12]([C:15]2[C:16]([F:21])=[N:17][CH:18]=[CH:19][CH:20]=2)=[CH:11][CH2:10]1)(C(C)(C)C)(C)C>ClCCl>[F:21][C:16]1[C:15]([C:12]2[CH2:13][CH2:14][CH:9]([OH:8])[CH2:10][CH:11]=2)=[CH:20][CH:19]=[CH:18][N:17]=1
Reactant: CC(C)(C)[Si](C)(C)OC1CC=C(c2cccnc2F)CC1
Solvent: ClCCl
Product: OC1CC=C(c2cccnc2F)CC1
Temperature: 0 °C

Procedure:
To a flask containing 3-(4-(tert-butyldimethylsilyloxy)cyclohex-1-enyl)-2-fluoropyridine (1.5 g, 4.88 mmol) was added anhydrous dichloromethane (48.8 mL) under nitrogen. After cooling to 0° C., hydrogen fluoride-pyridine complex (1.696 mL, 19.51 mmol) was added dropwise. The reaction mixture was warmed to room temperature and stirred until the starting material had been consumed. The reaction mixture was quenched with saturated aqueous sodium bicarbonate and extracted with dichloromethane before drying over magnesium sulfate, filtering, and concentrating to a clear oil under reduced pressure. The material was used without purification.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([CH3:9])[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:17][CH:18]=[C:19]([CH3:21])[CH3:20]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:17][CH:18]=[C:19]([CH3:21])[CH3:20])=[C:4]([CH3:9])[CH:3]=1
Reactant: Cc1cc(Br)ccc1O
Reactant: CC(C)=CCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Product: CC(C)=CCOc1ccc(Br)cc1C

Procedure:
Using essentially the same procedure as Example 5-20, Step 1, 4-bromo-2-methylphenol (1.00 g, 5.35 mmol), cesium carbonate (3.48 g, 10.7 mmol) and 4-bromo-2-methyl-2-butene (0.75 mL, 6.42 mmol) afforded the desired product as a pale-yellow oil.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[N:12]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:13]=[C:14]([C:16]#[N:17])[N:15]=2)=[O:10])=[C:4]([C:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]=2)[CH:3]=1.C([Sn](CCCC)(CCCC)[C:37]([O:39]CC)=[CH2:38])CCC.CCOC(C)=O>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:37]([C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[N:12]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:23])[CH3:24])[CH:13]=[C:14]([C:16]#[N:17])[N:15]=2)=[O:10])=[C:4]([C:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]=2)[CH:3]=1)(=[O:39])[CH3:38]
Reactant: C=C(OCC)[Sn](CCCC)(CCCC)CCCC
Reactant: C[Si](C)(C)CCOCn1cc(C#N)nc1C(=O)Nc1ccc(Br)cc1C1=CCCCC1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: CC(=O)c1ccc(NC(=O)c2nc(C#N)cn2COCC[Si](C)(C)C)c(C2=CCCCC2)c1
Temperature: 90 °C
Reaction time: 2 h
Yield: 86 %

Procedure:
A mixture of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid (4-bromo-2-cyclohex-1-enyl-phenyl)-amide (as prepared in the previous step, 100 mg, 0.199 mmol), tributyl(1-ethoxyvinyl)stannane (86.3 mg, 0.239 mmol) and Pd(PPh3)2Cl2 (10.5 mg, 0.0149 mmol) in 2 mL of 1,4-dioxane was stirred at 90° C. for 2 h under Ar. After cooling to RT, the reaction was treated with EtOAc (40 mL) and washed with 15% citric acid aqueous solution (2×10 mL), H2O (10 mL) and brine (10 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (10-20% EtOAc/hexane) to give 80.1 mg (86%) of the title compound as a light brown oil. Mass spectrum (ESI, m/z): Calcd. for C25H32N4O3Si, 465.2 (M+H). found 465.1.
Reaction SMILES: [CH2:1]([N:8]1[C:12](Br)=[C:11]([N+:14]([O-:16])=[O:15])[C:10]([Br:17])=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[CH2:19]([CH2:21][NH2:22])[OH:20]>>[CH2:1]([N:8]1[C:12]([NH:22][CH2:21][CH2:19][OH:20])=[C:11]([N+:14]([O-:16])=[O:15])[C:10]([Br:17])=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NCCO
Reactant: O=[N+]([O-])c1c(Br)nn(Cc2ccccc2)c1Br
Solvent: O
Product: O=[N+]([O-])c1c(Br)nn(Cc2ccccc2)c1NCCO

Procedure:
3.61 (10 mmoles) of 1-benzyl-3,5-dibromo-4-nitropyrazole are heated at 80° C. in 15 ml ethanolamine for 2 hours. After cooling, the reaction mixture is poured on 30 ml water and the separated precipitate is collected by filtration. After recrystallizing once from toluene, 2.5 g (74 percent of theory) of 1-benzyl-3-bromo-5-(2'-hydroxyethyl)amino-4-nitropyrazole are obtained in the form of pale yellow crystals with a melting point of 110° to 112° C.
Reaction SMILES: [CH3:1][C:2]1([CH3:17])[O:7][C:6](=[O:8])[N:5]([CH2:9][CH2:10][C:11]#[N:12])[C:4]2[CH:13]=[CH:14][CH:15]=[CH:16][C:3]1=2.[CH2:18]([Mg]Br)[CH3:19].B(F)(F)F.CCOCC.[OH-].[Na+]>C(OCC)C.CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4]>[NH2:12][C:11]1([CH2:10][CH2:9][N:5]2[C:4]3[CH:13]=[CH:14][CH:15]=[CH:16][C:3]=3[C:2]([CH3:17])([CH3:1])[O:7][C:6]2=[O:8])[CH2:19][CH2:18]1
Reactant: CC1(C)OC(=O)N(CCC#N)c2ccccc21
Reactant: CC[Mg]Br
Agent: [Ti+4]
Agent: CC(C)[O-]
Agent: FB(F)F
Solvent: CCOCC
Product: CC1(C)OC(=O)N(CCC2(N)CC2)c2ccccc21
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A suspension of 6.0 g (26 mmol) of 3-(4,4-dimethyl-2-oxo-4H-benzo[d][1,3]oxazin-1-yl]propionitrile in 120 mL of diethyl ether is combined with 16.5 mL (56 mmol) of titanium tetraisopropoxide while being cooled with an ice bath. Then 18.5 mL of a 3 molar solution of ethylmagnesium bromide in diethyl ether is added dropwise such that the temperature does not climb past 20° C. The mixture is stirred for 30 minutes at ambient temperature and 7.0 mL (55 mmol) boron trifluoride-diethyl ether is added batchwise while cooling with an ice bath. The mixture is stirred for one hour at ambient temperature and 150 mL of a 1 molar sodium hydroxide solution is added dropwise while cooling. The reaction mixture is diluted with diethyl ether and the phases are separated. The aqueous phase is extracted with diethyl ether and the combined organic phases are extracted with sodium sulfite solution and repeatedly extracted with 1 molar hydrochloric acid. The hydrochloric acid phases are combined, extracted with diethyl ether, made alkaline with sodium hydroxide solution, and exhaustively extracted with dichloromethane. The dichloromethane phases are dried with sodium sulfate and evaporated down. Light yellow oil. Yield: 1.5 g (22%); mass spectroscopy: [M+H]+=261.
Reaction SMILES: CC1CCC(C)C(C)(C)C=1C=O.CC(C)=O.O(C)[Na].[CH3:20][CH:21]1[C:26]([CH3:28])([CH3:27])[C@@H:25](/[CH:29]=[CH:30]/[C:31]([CH3:33])=[O:32])[C:24]([CH3:34])=[CH:23][CH2:22]1.CC1C(C)(C)[C@H](/C=C\C(C)=O)C(C)=CC1>C(O)C.CO>[CH3:20][CH:21]1[C:26]([CH3:27])([CH3:28])[C:25](/[CH:29]=[CH:30]/[C:31]([CH3:33])=[O:32])=[C:24]([CH3:34])[CH2:23][CH2:22]1
Reactant: CC(=O)/C=C/[C@H]1C(C)=CCC(C)C1(C)C
Agent: CC(=O)/C=C\[C@@H]1C(C)=CCC(C)C1(C)C
Agent: CC1=C(C=O)C(C)(C)C(C)CC1
Agent: CO[Na]
Solvent: CC(C)=O
Solvent: CCO
Solvent: CO
Product: CC(=O)/C=C/C1=C(C)CCC(C)C1(C)C
Yield: 76 %

Procedure:
On the other hand, addition of a solution of 3.0 g (19.74 mmol) of pure 2,5,6,6-tetramethyl-1-cyclohexen-1-carbaldehyde in 3 ml of ethanol and of 3 ml of acetone (41 mmol) to 4 ml (~22 mmol) of a 30% solution of NaOCH3 in methanol, the reaction having proceeded for 18 h at room temperature, provided, after the usual treatment and bulb-to-bulb distillation, a mixture (3.29 g) containing 34% of trans-α-irone, 6% of cis-α-irone and 50% of β-irone (yield 76%).
Reaction SMILES: [O:1]=[C:2]([CH2:9][CH2:10][CH2:11][CH3:12])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[H-].[Na+].Br[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([I:23])=[CH:19][CH:18]=1>CS(C)=O>[I:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][CH:3]([C:2](=[O:1])[CH2:9][CH2:10][CH2:11][CH3:12])[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[CH:18][CH:19]=1
Reactant: CCCCC(=O)CC(=O)OCC
Reactant: BrCc1ccc(I)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: CCCCC(=O)C(Cc1ccc(I)cc1)C(=O)OCC
Reaction time: 0.17 h
Yield: 28.9 %

Procedure:
To a solution of 3.77 g (43.8 mmol) ethyl 3-oxoheptanoate in 200 mL DMSO was added 1.75 g (43.8 mmol) 65% NaH in oil. After 10 minutes, 6.5 g (21.9 mmol) α-bromo-4-iodotoluene was added. The mixture was allowed to stir for 2 hours. It was then poured into an ice/brine mixture and extracted 3 times with ether. The combined organic material was washed with brine, dried over MgSO4,stripped of solvent in vacuo, then Still flash chromatographed in 40% CH2Cl2 /hexane to give 2.46 g of the title compound, 29% yield. Rf 0.23 in 40% CH2Cl2 /hexane, visualized by UV and ninhydrin stain; 1H-NMR (300 MHz, CDCl3): δ 7.58 (m,2H), 6.93 (m, 2H), 4.14 (m,2H), 3.72 (3 line m, 1H), 3.09 (m, 2H), 2.44 (12 line m, 2H), 1.50 (m, 2H), 1.22 (m, 2H), 1.21 (3 line m, 3H), 0.86 (3 line m, 3H).
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][OH:8])=[CH:5][CH:4]=1.[CH2:11](Br)[C:12]#[CH:13]>>[CH2:13]([O:1][CH2:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][OH:8])=[CH:5][CH:4]=1)[C:12]#[CH:11]
Reactant: OCc1ccc(CO)cc1
Reactant: C#CCBr
Product: C#CCOCc1ccc(CO)cc1

Procedure:
In an analogous manner to that described in Example 1, from 4-(hydroxymethyl)benzyl alcohol and propargyl bromide there is obtained 4-[(2-propynyloxy)methyl]benzyl alcohol. This alcohol is reacted in an analogous manner to that described in Example 2 with cyclopropane carboxylic acid chloride to give cyclopropane carboxylic acid p-[(2-propynyloxy)methyl]benzyl ester.
Reaction SMILES: Cl.[NH2:2][C:3]([CH2:8][OH:9])([CH2:6][OH:7])[CH2:4][OH:5].CO[C:12](OC)([CH3:14])[CH3:13].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.CN(C)C=O>C(OCC)(=O)C.C(N(CC)CC)C>[NH2:2][C:3]1([CH2:8][OH:9])[CH2:6][O:7][C:12]([CH3:14])([CH3:13])[O:5][CH2:4]1
Reactant: NC(CO)(CO)CO
Reactant: COC(C)(C)OC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: O
Product: CC1(C)OCC(N)(CO)CO1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
2-amino-2-(hydroxymethyl)propane-1,3-diol hydrochloride (320 g, 2.03 mol), 2,2-dimethoxypropane (240 g, 2.30 mol), and p-toluenesulfonic acid monohydrate (16.2 g, 102 mmol) were combined into anhydrous dimethylformamide (1.0 L). The solution was stirred vigorously by a mechanical stirrer for 48 hours at room temperature. Triethyl amine (300 mL) and ethyl acetate (1.5 L) were added. A white precipitate formed immediately. The white salt was filtered off and the low boiling point solvents were removed by a rotary evaporator. The product, (5-amino-2,2-dimethyl-1,3-dioxan-5-yl)methanol, was obtained by distillation (250 g, 76%), by 107° C./0.3 torr. 1H NMR (300 MHz, CDCl3) δ1.48 (s, 3H), 1.53 (s, 3H), 3.14 (br, 2H), 3.51 (s, 1H), 3.53 (d, 2H), 3.78 (d, 2H).
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:10]([O:22][CH3:23])=[CH:11][C:12]([N+:19]([O-])=O)=[C:13]([CH:18]=1)[C:14]([O:16][CH3:17])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O-]S(S([O-])=O)=O.[Na+].[Na+]>CO.O>[NH2:19][C:12]1[CH:11]=[C:10]([O:22][CH3:23])[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:18][C:13]=1[C:14]([O:16][CH3:17])=[O:15]
Reactant: COC(=O)c1cc(OCc2ccccc2)c(OC)cc1[N+](=O)[O-]
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COC(=O)c1cc(OCc2ccccc2)c(OC)cc1N

Procedure:
To a solution of methyl 5-(benzyloxy)-4-methoxy-2-nitrobenzoate (13.48 g, 0.0425 mol) in MeOH (700 mL) at 55° C., a concentrated solution of Na2S2O4 in water was added slowly until no more starting material was observed on TLC. The heterogeneous solution was concentrated under vacuum. The residue was treated with water (100 ml) and the mixture extracted with ethyl acetate (2×200 mL). The combined organic layers were washed with water and brine. After drying over MgSO4, the solvent was evaporated and the residue was purified on silica gel column, using ethyl acetate/DCM (1/9) as eluent to yield methyl 2-amino-5-(benzyloxy)-4-methoxybenzoate. Yield: 7.36 g (60%). 1HNMR (DMSO-d6): δ 7.34 (5H, m), 7.25 (1H, s), 6.48 (2H, s), 6.39 (1H, s), 4.91 (2H, s), 3.80 (3H, s), 3.73 (3H, s). LC-MS (ESI) m/z 288 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:24]([O:26]C)=[O:25])=[C:6]([NH:8][C:9](=[O:23])/[CH:10]=[CH:11]/[C:12]2[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:14][CH:13]=2)[CH:7]=1.[OH-].[Na+]>C(O)C>[C:24]([C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][C:6]=1[NH:8][C:9](=[O:23])/[CH:10]=[CH:11]/[C:12]1[CH:13]=[CH:14][C:15]([CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])=[CH:16][CH:17]=1)([OH:26])=[O:25]
Reactant: CCCCCc1ccc(/C=C/C(=O)Nc2cc(Cl)ccc2C(=O)OC)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCCCCc1ccc(/C=C/C(=O)Nc2cc(Cl)ccc2C(=O)O)cc1

Procedure:
Prepared analogously to Example 2 from trans-4-n-pentylcinnamic acid-N-(5-chloro-2-methoxycarbonyl-phenyl)-amide and sodium hydroxide solution in ethanol.
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][C:20]([Cl:31])=[N:21][C:22]([N:23]4[CH2:29][CH:28]5[O:30][CH:25]([CH2:26][CH2:27]5)[CH2:24]4)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)C1C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].Cl[C:39]([O:41][CH3:42])=[O:40]>ClCCCl>[CH:25]12[O:30][CH:28]([CH2:27][CH2:26]1)[CH2:29][N:23]([C:22]1[N:21]=[C:20]([Cl:31])[N:19]=[C:18]3[N:14]([CH:11]4[CH2:12][CH2:13][N:8]([C:39]([O:41][CH3:42])=[O:40])[CH2:9][CH2:10]4)[N:15]=[CH:16][C:17]=13)[CH2:24]2
Reactant: Clc1nc(N2CC3CCC(C2)O3)c2cnn(C3CCN(Cc4ccccc4)CC3)c2n1
Reactant: COC(=O)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCCl
Product: COC(=O)N1CCC(n2ncc3c(N4CC5CCC(C4)O5)nc(Cl)nc32)CC1
Temperature: 57.5 °C

Procedure:
A suspension of 1-(1-benzyl-piperidin-4-yl)-6-chloro-4-(8-oxa-3-aza-bicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidine (1.0 g, 2.3 mmol) and potassium carbonate (0.94 g, 6.8 mmol) in 1,2-dichloroethane (15 mL) was treated with methyl chloroformate (0.53 mL, 6.8 mmol) and then heated for two hours in a 55-60° C. oil bath. The mixture was filtered through a pad of diatomaceous earth, eluting with dichloromethane. The filtrate was concentrated to dryness under reduced pressure to furnish methyl 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate. MS (ES+): 407.5, 409.6 (M+H)+
Reaction SMILES: [C:1]1([CH:7]([OH:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(C1C=CC=CC=1)(=O)C.C1([C@H](O)C)C=CC=CC=1>>[C:1]1([C@@H:7]([OH:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(O)c1ccccc1
Agent: C[C@@H](O)c1ccccc1
Solvent: CC(=O)c1ccccc1
Product: C[C@H](O)c1ccccc1
Reaction time: 144 h
Yield: 60.7 %

Procedure:
As shown here, the biochemical conversion reaction of immobilized green pea protein for the substrate (±)-1-phenylethanol (201 mg) requires 6 days by going through bioconversion to acetophenone accompanying sterically selective oxidation of (R)-1-phenylethanol to obtain 122 mg of (S)-1-phenylethanol at a yield of 61%. Optical purity was obtained at 98% e.e.
Reaction SMILES: [C:1]([O:4][C@H:5]1[C@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@@H:10]([O:16][C:17](=[O:19])[CH3:18])[C@:9]2([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([CH2:28][C:29]4[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=4)[CH:22]=3)[O:20][C@@:6]1([CH2:36][O:37][C:38](=[O:40])[CH3:39])[CH2:7][O:8]2)(=[O:3])[CH3:2].CCN(C(C)C)C(C)C.Br[CH2:51][C:52]([C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:53]>C(#N)C.C(OC(=O)C)C>[C:1]([O:4][C@H:5]1[C@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@@H:10]([O:16][C:17](=[O:19])[CH3:18])[C@:9]2([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([CH2:28][C:29]4[CH:30]=[CH:31][C:32]([O:35][CH2:51][C:52](=[O:53])[C:54]5[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=5)=[CH:33][CH:34]=4)[CH:22]=3)[O:20][C@@:6]1([CH2:36][O:37][C:38](=[O:40])[CH3:39])[CH2:7][O:8]2)(=[O:3])[CH3:2]
Reactant: O=C(CBr)c1ccccc1
Reactant: CC(=O)OC[C@@]12CO[C@@](c3ccc(Cl)c(Cc4ccc(O)cc4)c3)(O1)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]2OC(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Solvent: CCOC(C)=O
Product: CC(=O)OC[C@@]12CO[C@@](c3ccc(Cl)c(Cc4ccc(OCC(=O)c5ccccc5)cc4)c3)(O1)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]2OC(C)=O
Reaction time: 8 h
Yield: 71.7 %

Procedure:
To a solution of (1R,2S,3S,4R,55)-1-(acetoxymethyl)-5-(4-chloro-3-(4-hydroxybenzyl)phenyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triyl triacetate (260 mg, 0.46 mmol) and DIPEA (0.38 mL, 2.25 mmol) in acetonitrile (2.25 mL), 2-bromo-1-phenylethanone (269 mg, 1.3 mmol) was added at r.t. and stirred overnight. After completion of the reaction as confirmed by TLC, the reaction mixture was diluted with ethylacetate (100 mL) and washed with water (20 mL) and brine (20 mL) successively. The organic layer was dried over Na2SO4 and the volatiles were evaporated in vacuo. The residue obtained was purified by column chromatography (silica gel, 2.2:7.8 acetone:hexane) to afford the title compound (230 mg, 0.33 mmol, 73.6%).