Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[Si:7]([O:14][CH2:15][C@@H:16]([OH:24])[CH2:17][C:18]#[C:19][Si](C)(C)C)([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]>CO>[Si:7]([O:14][CH2:15][C@@H:16]([OH:24])[CH2:17][C:18]#[CH:19])([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]
Reactant: CC(C)(C)[Si](C)(C)OC[C@@H](O)CC#C[Si](C)(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: C#CC[C@H](O)CO[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Potassium carbonate is added to a solution of (S)-1-(tert-butyldimethylsilyloxy)-5-(trimethylsilyl)pent-4-yn-2-ol in methanol and the mixture stirred at room temperature for 8 hours. The solvent is removed under reduced pressure, aqueous ammonium chloride solution added, and the mixture extracted with ethyl acetate (3×). The combined organic layers are washed with brine, dried (MgSO4), concentrated under reduced pressure and purified by flash chromatography (biotage; ethyl acetate/hexane gradient).
Reaction SMILES: [C:1]1(=[O:11])[O:6][C:4](=[O:5])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[NH3:12]>>[C:1]([OH:6])(=[O:11])[C:2]1[C:3](=[CH:7][CH:8]=[CH:9][CH:10]=1)[C:4]([NH2:12])=[O:5]
Reactant: O=C1OC(=O)c2ccccc21
Reactant: N
Product: NC(=O)c1ccccc1C(=O)O
Temperature: 25 °C

Procedure:
With vigorous stirring, concentrated ammonia solution (900 ml, S.G. 0.9) was treated portionwise with phthalic anhydride (600 g, 4.0 moles) over a period of 11/2 hrs. After the reaction mixture had cooled to room temperature, the precipitated ammonium phthalamate was filtered, then dissolved in the minimum of water. When this solution was acidified to pH 2, phthalamic acid began to crystalize, M.P. 132°-6°.
Reaction SMILES: O[CH:2]=[C:3]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=3)=[CH:9][CH:10]=2)[NH:5][C:4]1=[O:20].[N:21]1([C:27]2[CH:32]=[CH:31][C:30]([NH2:33])=[CH:29][CH:28]=2)[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1>O1CCCC1>[CH3:19][O:18][C:14]1[CH:13]=[C:12]([C:8]2[CH:7]=[C:6]3[C:11]([C:3](=[CH:2][NH:33][C:30]4[CH:29]=[CH:28][C:27]([N:21]5[CH2:22][CH2:23][O:24][CH2:25][CH2:26]5)=[CH:32][CH:31]=4)[C:4](=[O:20])[NH:5]3)=[CH:10][CH:9]=2)[CH:17]=[CH:16][CH:15]=1
Reactant: Nc1ccc(N2CCOCC2)cc1
Reactant: COc1cccc(-c2ccc3c(c2)NC(=O)C3=CO)c1
Solvent: C1CCOC1
Product: COc1cccc(-c2ccc3c(c2)NC(=O)C3=CNc2ccc(N3CCOCC3)cc2)c1
Temperature: 25 °C

Procedure:
The named compound is prepared by refluxing 0.020 gms E & Z 3-hydroxymethylene-6-(3-methoxy-phenyl)-1,3-dihydro-indol-2-one with 0.020 gms. 4-morpholin-4-yl-phenylamine in tetrahydrofuran (0.33 mL) for 2 days. Following cooling to room temperature, solvent evaporation in vacuo, trituration with isopropanol and filtration the reaction yields the named compound as a solid in the amount of 15.7 mg.
Reaction SMILES: C[C:2]1[CH:3]=[CH:4][C:5]([N:11]2[N:15]=[CH:14][CH:13]=[N:12]2)=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].[CH3:16]C1C(C(O)=O)=C(I)C=CC=1.N1C=CN=N1>>[CH3:16][C:10]1[CH:2]=[CH:3][CH:4]=[C:5]([N:11]2[N:12]=[CH:13][CH:14]=[N:15]2)[C:6]=1[C:7]([OH:9])=[O:8]
Reactant: Cc1cccc(I)c1C(=O)O
Reactant: Cc1ccc(-n2nccn2)c(C(=O)O)c1
Agent: c1c[nH]nn1
Product: Cc1cccc(-n2nccn2)c1C(=O)O

Procedure:
The title compound was prepared following the same general protocol as described for 5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoic acid in Example A11 using 6-methyl-2-iodobenzoic acid and 1,2,3-triazole. ESI-MS (m/z): 204 [M+1]+.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[N:5][N:6]2[C:11]([CH3:12])=[CH:10][C:9]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=3)=[N:8][C:7]=12)#[CH:2].[NH2:23][C:24]1[CH:29]=[CH:28][C:27](Br)=[CH:26][N:25]=1>>[CH3:12][C:11]1[N:6]2[N:5]=[CH:4][C:3]([C:1]#[C:2][C:27]3[CH:28]=[CH:29][C:24]([NH2:23])=[N:25][CH:26]=3)=[C:7]2[N:8]=[C:9]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:21])([F:22])[F:20])=[CH:15][CH:14]=2)[CH:10]=1
Reactant: Nc1ccc(Br)cn1
Reactant: C#Cc1cnn2c(C)cc(-c3ccc(C(F)(F)F)cc3)nc12
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc2c(C#Cc3ccc(N)nc3)cnn12

Procedure:
The title compound was prepared from 3-ethynyl-7-methyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (example C.12) (151 mg, 0.5 mmol) and 2-amino-5-bromopyridine (87 mg, 0.5 mmol) according to general procedure II. Obtained as an orange solid (37 mg, 19%). MS (ISP) 394.0 [(M+H)+].
Reaction SMILES: [CH2:1](Br)[CH:2]=[CH2:3].[CH3:5][C:6]1[CH2:11][CH2:10][CH2:9][C:8]([CH3:13])([CH3:12])[C:7]=1[CH:14]=[O:15]>CCOCC>[CH3:5][C:6]1[CH2:11][CH2:10][CH2:9][C:8]([CH3:12])([CH3:13])[C:7]=1[CH:14]([OH:15])[CH2:3][CH:2]=[CH2:1]
Reactant: CC1=C(C=O)C(C)(C)CCC1
Reactant: C=CCBr
Solvent: CCOCC
Product: C=CCC(O)C1=C(C)CCCC1(C)C
Temperature: 0 °C
Yield: 57 %

Procedure:
In a typical experiment 10.7 g. of Mg turnings and 5 g. of allyl bromide were allowed to react in 70 ml. of dry ether. The reaction was exothermic and the temperature of the reaction mixture increased up to the boiling point of the solvent. To this solution allyl bromide (46 g.) and β-cyclocitral (61 6.) in 160 ml. of ether were added with vigorous stirring at such a rate as to maintain the ether at the boiling temperature. The reaction mixture was then kept at reflux during 6 hours and after cooling it was poured into a ice-cold concentrated aqueous solution of NH4C1. The ethereal layer after the usual treatments gave 2,6,6-trimethyl-1-[1-hydroxy-3-butenyl]-1-cyclohexene (44.5 g; 57 % yield): B.p. 60°-2° /0.001 Torr; nD20 = 1.4964; d420 = 0.9398.
Reaction SMILES: [C:1]([O:5][C:6](=[O:29])[NH:7][CH:8]([CH2:25][CH:26]([CH3:28])[CH3:27])[CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]2[C:24]3[C:19](=[CH:20][N:21]=[CH:22][CH:23]=3)[CH2:18][O:17][C:15]=2[CH:16]=1)([CH3:4])([CH3:3])[CH3:2].C1C(=O)N([Br:37])C(=O)C1>C(#N)C>[Br:37][C:12]1[C:11]([O:10][CH2:9][C@@H:8]([NH:7][C:6](=[O:29])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:25][CH:26]([CH3:27])[CH3:28])=[CH:16][C:15]2[O:17][CH2:18][C:19]3[C:24]([C:14]=2[CH:13]=1)=[CH:23][CH:22]=[N:21][CH:20]=3
Reactant: CC(C)CC(COc1ccc2c(c1)OCc1cnccc1-2)NC(=O)OC(C)(C)C
Reactant: O=C1CCC(=O)N1Br
Solvent: CC#N
Product: CC(C)C[C@@H](COc1cc2c(cc1Br)-c1ccncc1CO2)NC(=O)OC(C)(C)C
Reaction time: 0.03 h
Yield: 38.7 %

Procedure:
A solution of tert-butyl(1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (0.072 g, 0.181 mmol) in acetonitrile (5 mL) cooled to 0° C. and stirred for 2 min. NBS (0.029 g, 0.163 mmol) was added in single portion and the reaction mixture stirred at 0° C. for 2 h. The solvent was removed under reduced pressure and water 10 mL) was added. The product was extracted with ethyl acetate (3×15 mL). The combined organic extracts were washed with water (1×20 mL) dried over sodium sulfate and concentrated under reduced pressure. The residue was purified via preparative TLC (40% EtOAc:pet ether) to obtain (S)-tert-butyl 1-(9-bromo-5H-chromeno[3,4-c]pyridin-8-yloxy)-4-methylpentan-2-ylcarbamate (30 mg, 0.063 mmol, 35% yield). 1H NMR (400 MHz, CD3OD) δ 8.48 (d, J=5.4 Hz, 1H), 8.38 (s, 1H), 8.07 (s, 1H), 7.68 (d, J=5.4 Hz, 1H), 6.73 (s, 1H), 5.21 (s, 2 H), 4.02-3.98 (m, 3H), 1.92-1.71 (m, 1H), 1.56-1.52 (m, 2H), 0.97 (t, J=6.8 Hz, 6H).
Reaction SMILES: [OH:1][C:2]1([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2OS(C(F)(F)F)(=O)=O)[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[Cl:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC1CCCO1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:30][C:31]1[CH:36]=[CH:35][C:34]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[CH2:15][C:2]2([OH:1])[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])[CH2:4][CH2:3]2)=[CH:33][CH:32]=1
Reactant: CC(C)(C)OC(=O)N1CCC(O)(Cc2ccccc2OS(=O)(=O)C(F)(F)F)CC1
Reactant: OB(O)c1ccc(Cl)cc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=P([O-])([O-])[O-]
Solvent: CC1CCCO1
Product: CC(C)(C)OC(=O)N1CCC(O)(Cc2ccccc2-c2ccc(Cl)cc2)CC1

Procedure:
A mixture of EXAMPLE 263D (4.3 g), 4-chlorophenylboronic acid (1.84 g), K3PO4 (2.91 g), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.36 g) in 2-methyltetrahydrofuran (50 mL) was stirred at 70° C. for 24 hours. The reaction was cooled and quenched with water (50 mL), extracted twice with ether, and the combined extracts were washed with brine, dried over Na2SO4, filtered, and concentrated. The crude product was chromatographed on silica gel using 5-30% ethyl acetate in hexanes to provide the title compound.
Reaction SMILES: C(O)=O.[CH2:4]([NH:11][CH2:12][CH2:13]O)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.Br[CH2:16][C:17]([C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=1[Cl:26])=[O:18]>C(Cl)Cl>[CH2:4]([N:11]1[CH2:12][CH2:13][O:18][CH:17]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[Cl:26])[CH2:16]1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: O=C(CBr)c1ccc(F)cc1Cl
Reactant: OCCNCc1ccccc1
Solvent: O=CO
Solvent: ClCCl
Product: Fc1ccc(C2CN(Cc3ccccc3)CCO2)c(Cl)c1
Reaction time: 20 h
Yield: 99.7 %

Procedure:
Combine formic acid (98-100%; 0.30 mL, 8 mmol) and 2-benzylaminoethanol (1.21 g, 8 mmol) and cool the resulting mixture with an ice bath. Add 2-bromo-1-(2-chloro-4-fluoro-phenyl)ethanone (1.0 g, 4 mmol); heat the mixture to reflux; and stir at that temperature for 20 h. Dilute the mixture with DCM and wash with saturated aqueous Na2CO3 solution. Dry organic phases over MgSO4; filter; collect the filtrate; and concentrate under reduced pressure. Purify via flash column chromatography eluting with a gradient of 0-20% methyl tertiary-butyl ether in hexanes. Combine the product fractions and remove the solvents under reduced pressure to give the title compound as a yellow oil (1.22 g, 43%). MS (m/z): 306 (M+1).
Reaction SMILES: C[O:2][C:3](=[O:27])[CH:4]([C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH:20]=[CH:19][CH:18]=2)=[CH:13][CH:12]=1)[CH2:5][CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1.[OH-].[Li+]>O1CCCC1>[CH:6]1([CH2:5][CH:4]([C:11]2[CH:12]=[CH:13][C:14]([C:17]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[CH:20]=[CH:19][CH:18]=3)=[CH:15][CH:16]=2)[C:3]([OH:27])=[O:2])[CH2:10][CH2:9][CH2:8][CH2:7]1
Reactant: COC(=O)C(CC1CCCC1)c1ccc(-c2cccc3ccccc23)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=C(O)C(CC1CCCC1)c1ccc(-c2cccc3ccccc23)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 54.6 %

Procedure:
A solution of 3-cyclopentyl-2-(4-naphthalen-1-yl-phenyl)-propionic acid methyl ester (3.32 g, 9.26 mmol) in tetrahydrofuran (12 mL) was treated with a 0.8M aqueous lithium hydroxide solution (12 mL). The resulting reaction mixture was stirred at 25° C. for 24 h, at which time, thin layer chromatography indicated the presence of starting material. The reaction mixture was then heated at 80° C. for 18 h. The reaction mixture was then allowed to cool to 25° C. and concentrated in vacuo to remove tetrahydrofuran. The residue was acidified to pH=2 with a 10% aqueous hydrochloric acid solution and then extracted with ethyl acetate (2×150 mL). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70-230 mesh, 3/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(4-naphthalen-1-yl-phenyl)-propionic acid (1.74 g, 55%) as a white foam: mp 63-64° C.; EI-HRMS m/e calcd for C24H24O2 (M+) 344.1776, found 344.1770.
Reaction SMILES: [CH2:1]([CH:5]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[CH2:6][OH:7])[CH2:2][CH2:3][CH3:4].[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.C([O-])(=O)C.[Na+]>ClCCl>[CH2:1]([CH:5]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][Si:14]([C:17]([CH3:18])([CH3:20])[CH3:19])([CH3:15])[CH3:16])[CH:6]=[O:7])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCC(CO)CCCCCO[Si](C)(C)C(C)(C)C
Agent: O=[Cr](=O)([O-])Cl
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: ClCCl
Product: CCCCC(C=O)CCCCCO[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Yield: 88 %

Procedure:
A solution of 2-butyl-7-(tert-butyldimethylsilyloxy)-1-heptanol in dichloromethane (10 ml) was added to a suspension of pyridinium chlorochromate (8.09 g, 38 mmol) and sodium acetate (150 mg) in 30 ml of dichloromethane and stirred at ambient temperature for several hours. After the usual work up followed by PMPLC, 6.61 g (88%) of 2-butyl-7-(tert-butyldimethylsilyloxy)heptanaI was obtained.
Reaction SMILES: [C:1]([O:5][C:6](=[O:23])[NH:7][C@H:8]([C:13]([N:15]1[CH2:19][CH:18]=[CH:17][C@H:16]1[C:20](=O)[NH2:21])=[O:14])[C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:4])([CH3:3])[CH3:2].P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1>[C:1]([O:5][C:6](=[O:23])[NH:7][C@H:8]([C:13]([N:15]1[CH2:19][CH:18]=[CH:17][C@H:16]1[C:20]#[N:21])=[O:14])[C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)N[C@H](C(=O)N1CC=C[C@H]1C(N)=O)C(C)(C)C
Solvent: c1ccncc1
Solvent: O=P(Cl)(Cl)Cl
Product: CC(C)(C)OC(=O)N[C@H](C(=O)N1CC=C[C@H]1C#N)C(C)(C)C
Temperature: 0 °C
Yield: 84.3 %

Procedure:
(175 mg, 0.54 mmol) of (2) was dissolved in 4 ml of pyridine and the mixture was cooled to 0° C. Phosphorus oxychloride (0.2 ml, 2.15 mmol) was added dropwise and after 10 minutes of stirring the reaction mixture was poured into 20 ml of ice water and the organic material was extracted into 5×10 ml of ethyl acetate. The combined organic extract was washed with 2×20 ml of water, 1×20 ml of brine and dried over magnesium sulphate. The solvent was evaporated to afford 140 mg of (S,S) [1-(2-Cyano-2,5-dihydro-pyrrole-1-carbonyl)-2,2-dimethyl-propyl]-carbamic acid tert-butyl ester (3). Oil, 85% yield. 1H-NMR (CDCl3, 200 MHz) δ: 1.05 (s, 9H); 1.42 (s, 9H); 4.22 (d, 1H); 4.39-4.53 (m, 1H); 4.65-4.77 (m, 1H); 5.30 (d, 1H); 5.41-5.48 (m, 1H); 5.83-5.90 (m, 1H); 6.09-6.15 (m, 1H).
Reaction SMILES: [BH4-].[Na+].[CH3:3][C:4]1[CH:5]=[C:6]([C:22](=[O:39])[CH:23]([N:25]2[CH2:30][CH2:29][C:28]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)([OH:31])[CH2:27][CH2:26]2)[CH3:24])[CH:7]=[C:8]([CH3:21])[C:9]=1[O:10][Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13]>C(O)C>[CH3:3][C:4]1[CH:5]=[C:6]([C@@H:22]([OH:39])[C@H:23]([N:25]2[CH2:30][CH2:29][C:28]([C:32]3[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=3)([OH:31])[CH2:27][CH2:26]2)[CH3:24])[CH:7]=[C:8]([CH3:21])[C:9]=1[O:10][Si:11]([CH:15]([CH3:16])[CH3:17])([CH:12]([CH3:13])[CH3:14])[CH:18]([CH3:19])[CH3:20]
Reactant: Cc1cc(C(=O)C(C)N2CCC(O)(c3ccc(F)cc3)CC2)cc(C)c1O[Si](C(C)C)(C(C)C)C(C)C
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: Cc1cc([C@@H](O)[C@@H](C)N2CCC(O)(c3ccc(F)cc3)CC2)cc(C)c1O[Si](C(C)C)(C(C)C)C(C)C
Reaction time: 0.17 h
Yield: 40.3 %

Procedure:
A mixture of sodium borohydride (0.065 g, 1.72 mmol) and ethanol (5 mL) was stirred 10 min and then 1-(3,5-dimethyl-4-triisopropylsilyloxyphenyl)-2-(4-(4-fluoro-phenyl)-4-hydroxypiperidin-1-yl)-propan-1-one (0.90 g, 1.71 mmol in 25 mL of ethanol) was added. The reaction was stirred at ambient temperature over the weekend. The white solid which precipitated was collected by filtration and dried to yield 0.365 g (40%) of (1R*,2R*)-1-(3,5-dimethyl-4-triisopropylsilyloxyphenyl)-2-(4-(4-fluorophenyl)-4-hydroxypiperdin-1-yl)-propan-1-ol which was suitable for use without further purification and had: mp 186.5-187° C. Analysis calculated for C31H48FNO3Si.0.125 H2O: C, 69.69; H, 9.15; N, 2.62. Found: C, 69.65; H, 9.29; N, 2.57.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][CH:16]=1)[N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH3:6].C([Li])CCC.[S:22](Cl)([Cl:25])(=[O:24])=[O:23]>C1COCC1>[C:10]([O:9][C:7]([N:5]([CH3:6])[C:4]1[CH:14]=[CH:15][CH:16]=[C:2]([S:22]([Cl:25])(=[O:24])=[O:23])[CH:3]=1)=[O:8])([CH3:13])([CH3:12])[CH3:11]
Reactant: CN(C(=O)OC(C)(C)C)c1cccc(Br)c1
Reactant: O=S(=O)(Cl)Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CN(C(=O)OC(C)(C)C)c1cccc(S(=O)(=O)Cl)c1
Temperature: -78 °C
Reaction time: 0.25 h

Procedure:
3-Bromo-N-tert-butoxycarbonyl-N-methylaniline (0.358 g, 1.2 mmol) was dissolved in freshly distilled THF (5 ml) under a N2 atmosphere. The solution was chilled to −78° C. and n-butyl lithium (0.750 ml, 2.0 M solution in cyclohexane, 1.5 mmol) was added. After 15 minutes, sulfuryl chloride (0.121 ml, 1.5 mmol) was added and the reaction was allowed to warm to room temperature and stirring was continued overnight. THF was removed by evaporation and the resulting residue was diluted in EtOAc. Organic phase was washed with H2O and brine before being dried with MgSO4. The solvent was removed in vacuo. Purification by flash chromatography (1:19/EtOAc/Hex gradient to 1:9 and then to 1:4). Recovered 0.089 g (23%) of the product as a colorless oil. Rf=0.14 (1:9 EtOAc/Hex). 1H NMR (CDCl3) 7.96 (1H,s), 7.80 (1H,d), 7.68 (1H,d), 7.57 (1H,t), 3.33 (3H,s), 1.50 (9H,s).
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[O:12][S:13]([C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1)(=[O:15])=[O:14])([CH3:3])[CH3:2].[N+:23]([O-])([OH:25])=[O:24]>CC(O)=O>[CH:1]([C:4]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([N+:23]([O-:25])=[O:24])=[CH:6][C:5]=1[O:12][S:13]([C:16]1[CH:17]=[CH:18][C:19]([CH3:22])=[CH:20][CH:21]=1)(=[O:15])=[O:14])([CH3:3])[CH3:2]
Reactant: COc1ccc(OS(=O)(=O)c2ccc(C)cc2)c(C(C)C)c1
Reactant: O=[N+]([O-])O
Solvent: CC(=O)O
Product: COc1cc(C(C)C)c(OS(=O)(=O)c2ccc(C)cc2)cc1[N+](=O)[O-]
Yield: 98 %

Procedure:
To a solution of toluene-4-sulfonic acid 2-isopropyl-4-methoxy-phenyl ester (19.00 g, 59 mmol) in 118 mL AcOH was added 236 ml fuming HNO3 over 20 min. After 16 h the solution was pouring into a rapidly stirring slurry of 2 l of ice/H2O. After 15 min the precipitate was filtered, washed with H2O and dried under vacuum (50° C.) to give toluene-4-sulfonic-acid 2-isopropyl-4-methoxy-5-nitro-phenyl ester (21.27 g, 98%) and toluene-4-sulfonic acid 2-isopropyl-4-methoxy-3-nitro-phenyl ester and as a pale yellow solid (7:1 inseperable mixture).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][C:12]([OH:14])=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].S(Cl)(Cl)=O.[CH2:19]([CH2:21][NH2:22])[OH:20].C(=O)([O-])[O-].[K+].[K+]>C(Cl)(Cl)Cl.O.CN(C)C=O>[OH:20][CH2:19][CH2:21][NH:22][C:12](=[O:14])[CH2:11][CH2:10][C:7]1[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=1
Reactant: NCCO
Reactant: O=C(O)CCc1ccc([N+](=O)[O-])cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClC(Cl)Cl
Solvent: O=S(Cl)Cl
Solvent: CN(C)C=O
Product: O=C(CCc1ccc([N+](=O)[O-])cc1)NCCO
Yield: 76.6 %

Procedure:
60 g of 3-(4-nitrophenyl)propionic acid were suspended in 360 ml of chloroform, followed by the addition of 2.25 g of dimethylformamide. The thus-prepared reaction mixture was heated at 50°-60° C., to which 33.5 ml of thionyl chloride were gradually added dropwise. After the dropwise addition, the resultant mixture was heated under reflux for 1 hour, the solvent was distilled off under reduced pressure, and the resultant oily substance was dissolved in 150 ml of chloroform. The chloroform solution was added dropwise under ice cooling into a solution which had been formed by dissolving 28.2 g of ethanolamine and 42.5 g of potassium carbonate in 450 ml of water. After completion of the dropwise addition, the resultant mixture was stirred for 1 hour. Precipitated crystals were collected by filtration and then recrystallized from 1 of ethyl acetate, thereby obtaining 56.1 g of N-(2-hydroxyethyl)-3-(4-nitrophenyl)propionamide as crystals.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([CH2:16][CH2:17][C:18]2([CH3:25])[NH:22][C:21](=[O:23])[NH:20][C:19]2=[O:24])[CH:8]=[C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:10]=1[OH:11])([CH3:4])([CH3:3])[CH3:2].[CH2:26]([O:28][C:29](=[O:32])[CH:30]=[CH2:31])[CH3:27].[OH-].C([N+](C)(C)C)C1C=CC=CC=1.C(O)(=O)C>C(O)C.CO.O>[C:12]([C:9]1[CH:8]=[C:7]([CH2:16][CH2:17][C:18]2([CH3:25])[NH:22][C:21](=[O:23])[N:20]([CH2:31][CH2:30][C:29]([O:28][CH2:26][CH3:27])=[O:32])[C:19]2=[O:24])[CH:6]=[C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])[C:10]=1[OH:11])([CH3:15])([CH3:14])[CH3:13]
Reactant: CC1(CCc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)NC(=O)NC1=O
Reactant: C=CC(=O)OCC
Agent: C[N+](C)(C)Cc1ccccc1
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: CCO
Product: CCOC(=O)CCN1C(=O)NC(C)(CCc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)C1=O
Yield: 74.6 %

Procedure:
30 g (0.087 mol) of 5-(3',5'-di-tert.-butyl-4'-hydroxyphenylethyl)-5-methyl-hydantoin and 13.1 g (0.131 mol) of acrylic acid ethyl ester are dissolved in 100 ml of ethanol, 2 ml of a 40% strength solution of benzyl-trimethyl-ammonium hydroxide in methanol are added and the mixture is heated under reflux for 12 hours, whilst stirring. Thereafter it is neutralised with glacial acetic acid, diluted with 50 ml of water and cooled whilst stirring. The precipitate formed is filtered off, washed with 50% strength ethanol and recrystallised from 70% strength alcohol. 29 g of 5-(3',5'-ditert.-butyl-4'-hydroxy-phenylethyl)-5-methyl-3-ethoxycarbonylethyl-hydantoin of melting point 100° C are thus obtained. (Stabiliser No. 9).
Reaction SMILES: P([O-])([O-])([O-])=O.[CH2:6]([N:9]1[CH:13]([CH2:14][CH2:15][CH3:16])[CH2:12][O:11][S@@:10]1=[O:17])[CH2:7][CH3:8].I([O-])(=O)(=O)=[O:19].[Na+]>C(OCC)(=O)C.O.[Ru](=O)=O>[CH2:6]([N:9]1[C@@H:13]([CH2:14][CH2:15][CH3:16])[CH2:12][O:11][S:10]1(=[O:19])=[O:17])[CH2:7][CH3:8]
Reactant: CCCC1CO[S@](=O)N1CCC
Reactant: [O-][I+3]([O-])([O-])[O-]
Agent: O=[Ru]=O
Agent: O=P([O-])([O-])[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Product: CCC[C@H]1COS(=O)(=O)N1CCC
Yield: 93.7 %

Procedure:
Ruthenium dioxide hydrate (3 mg) and a phosphate buffer solution (pH 7.4, 28.7 mL) were subsequently added to a solution of (S)-3,4-dipropyl-1,2,3-oxathiazolidine 2-oxide (5.74 g) in ethyl acetate (46 mL) under ice-cooling and stirring. Sodium periodate (7.06 g) was added to the solution under ice-cooling and stirring, and then vigorously stirred at room temperature for 30 minutes. The suspension was filtered, and the insoluble matter was washed with ethyl acetate (17 mL). The filtrate and the washings were combined. The organic layer was separated and washed subsequently with a saturated aqueous sodium hydrogen carbonate solution (11.5 mL), an aqueous 10% sodium thiosulfate solution (11.5 mL) and a saturated aqueous sodium chloride solution (11.5 mL). Anhydrous sodium sulfate and activated carbon (0.57 g) were added to the organic layer and stirred at room temperature for 1 hour. The suspension was filtered, and the filtrate was concentrated under reduced pressure. The residue was added with tetrahydrofuran (8.6 mL) and concentrated under reduced pressure at 40° C. or lower to give (S)-3,4-dipropyl-1,2,3-oxathiazolidine 2,2-dioxide (5.83 g, 94% yield) as an orange-brown oil.
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:15])=[CH:4][C:5]2[O:10][C:9]([CH3:12])([CH3:11])[CH2:8][CH:7](O)[C:6]=2[CH:14]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1(C)C=CC=CC=1>[Br:1][C:2]1[C:3]([CH3:15])=[CH:4][C:5]2[O:10][C:9]([CH3:11])([CH3:12])[CH:8]=[CH:7][C:6]=2[CH:14]=1
Reactant: Cc1cc2c(cc1Br)C(O)CC(C)(C)O2
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: Cc1cc2c(cc1Br)C=CC(C)(C)O2

Procedure:
A stirred solution of the product of step d (27.1 g) in dry toluene (300 ml) is treated with p-toluenesulphonic acid (1.15 g) and heated under reflux for 2 h with water formed being removed via a Dean-Stark apparatus. The cooled solution is washed with aqueous sodium carbonate (100 ml, 2M), dried (Na2SO4), filtered and the solvent is evaporated off under reduced pressure to yield the crude product. This is purified by chromatography (silica gel, hexane) to give the title compound as an oil.