Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][CH:17]([CH3:36])[C:18]([N:20]([CH2:30][CH:31](OC)OC)[CH2:21][CH2:22][CH2:23][N:24]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]2)=[O:19])[CH:12]=[CH:13][C:14]=1[Cl:15].C([SiH](CC)CC)C.C(N(CC)CC)C>C(Cl)Cl>[Cl:8][C:9]1[CH:10]=[C:11]([N:16]2[CH2:31][CH2:30][N:20]([CH2:21][CH2:22][CH2:23][N:24]3[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]3)[C:18](=[O:19])[CH:17]2[CH3:36])[CH:12]=[CH:13][C:14]=1[Cl:15]
Reactant: COC(CN(CCCN1CCCCC1)C(=O)C(C)Nc1ccc(Cl)c(Cl)c1)OC
Agent: CC[SiH](CC)CC
Solvent: CCN(CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC1C(=O)N(CCCN2CCCCC2)CCN1c1ccc(Cl)c(Cl)c1
Temperature: 0 °C
Yield: 71.5 %

Procedure:
Trifluoroacetic acid (1.15 g, 10.1 mmol) was added to a solution of 2-(3,4-dichloro-phenylamino)-N-(2,2-dimethoxy-ethyl)-N-(3-piperidin-1-yl-propyl)-propionamide (300 mg, 0.67 mmol) in CH2Cl2 (6 mL) at 0° C. After 30 min the ice bath was removed, then after 1 h triethylsilane (391 mg, 3.36 mmol) was added. After 16 h the reaction mixture was cooled to 0° C. and treated with triethylamine, then after 15 min partitioned between CH2Cl2 and sat. aq. NaHCO3 solution. The organic layer was washed with brine, dried (MgSO4), and evaporated. Chromatography (IST Isolute® Flash NH2; EtOAc) afforded the title compound (184 mg, 71%). Yellow oil, MS: 384.2 (M+H)+.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][C:7]([O:9]CC)=[O:8].[OH-].[Li+]>C(O)C>[Cl:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][C:7]([OH:9])=[O:8]
Reactant: CCOC(=O)CCOCCCl
Agent: [Li+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)CCOCCCl
Temperature: 25 °C
Reaction time: 4 h

Procedure:
2.00 g (11.1 mmol) ethyl 3-(2-chloro-ethoxy)-propionate are suspended in 8 ml of ethanol and 4.96 ml (16.6 mmol) of 8% lithium hydroxide solution are added. The mixture is stirred for 4 hours at ambient temperature, then evaporated down i. vac., acidified with 2-molar hydrochloric acid, combined with diethyl ether and dried over sodium sulphate. Then it is filtered off and evaporated down i. vac.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]([CH3:18])[CH2:5][CH:6]([OH:17])[CH2:7][C:8]1([N+:14]([O-])=O)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1>[Ni].CO>[NH2:14][C:8]1([CH2:7][CH:6]([OH:17])[CH2:5][N:4]([CH2:3][CH2:2][OH:1])[CH3:18])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1
Reactant: CN(CCO)CC(O)CC1([N+](=O)[O-])CCCCC1
Agent: [Ni]
Solvent: CO
Product: CN(CCO)CC(O)CC1(N)CCCCC1
Temperature: 25 °C
Reaction time: 1.25 h
Yield: 34.8 %

Procedure:
A 300 mL Parr autoclave is charged with methanol (100 mL), Raney Nickel catalyst (R-3111, 6.8 g wet weight) and compound (13) (20.8 g crude) dissolved in 100 mL MeOH. The reactor is sealed, purged with nitrogen followed by purging with hydrogen and then brought up to 60° C. under 400 psi hydrogen pressure. When the temperature reaches 60° C., the reactor pressure is increased to approximately 450 psi. The reaction is stopped when no more hydrogen is consumed in the reaction. The entire reaction takes 1-1.5 h to reach completion. After cooling to room temperature, the reactor is vented, opened and the catalyst isolated via vacuum filtration. The brown filtrate is stripped on a rotary evaporator (50-55° C./28-29″ vacuum) to remove water/methanol. The above process provides 6.4 g of the crude mixture. The desired material, compound (14) is eluted in GC-MS EI at retention time of 22.7 minutes, however the molecular ion peak cannot not be seen due to fragmentation in the GC. The presence of 1-(1-aminocyclohexyl)-3-((2 hydroxyethyl) (methyl)amino)propan-2-ol (14) is identified by LC/MS with [M+H]=231.20.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]#[N:20])[CH:14]=2)[CH:10]([OH:12])[CH3:11])=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]#[N:20])[CH:14]=2)[CH:10]([O:12][S:29]([CH3:28])(=[O:31])=[O:30])[CH3:11])=[CH:4][CH:3]=1
Reactant: CS(=O)(=O)Cl
Reactant: CC(O)C(Cc1ccc(Cl)cc1)c1cccc(C#N)c1
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: CC(OS(C)(=O)=O)C(Cc1ccc(Cl)cc1)c1cccc(C#N)c1
Reaction time: 0.08 h

Procedure:
To a solution of 4-(4-chlorophenyl)-3-(3-cyanophenyl)-2-butanol (1.0 kg, 3.5 mol) in toluene (10 L) at 0° C. was added triethylamine (684 mL, 4.9 mol) and methanesulfonyl chloride (353 mL, 4.6 mol). After stirring for 5 min, the reaction mixture was filtered, and the precipitate was washed with toluene (8 L). The filtrate was washed with sodium bicarbonate (6 L, 50% saturated aqueous solution) and water (3 L), and concentrated to give the title compound.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][N:3]=1.[NH2:12][CH2:13][CH2:14][CH2:15][OH:16].O>C1COCC1.CC(C)([O-])C.[K+]>[F:9][C:8]([F:11])([F:10])[C:5]1[CH:6]=[CH:7][C:2]([O:16][CH2:15][CH2:14][CH2:13][NH2:12])=[N:3][CH:4]=1
Reactant: NCCCO
Reactant: Fc1ccc(C(F)(F)F)cn1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: NCCCOc1ccc(C(F)(F)F)cn1
Temperature: 0 °C

Procedure:
2-Fluoro-5-trifluoromethylpyridine (1.831 g, 11 mmol) was dissolved in anhydrous THF (15 mL) with stirring under nitrogen and cooled to 0° C. in an ice bath. To this was added dropwise over 30 minutes a solution of 3-amino-1-propanol (0.76 mL, 10 mmol) in anhydrous THF (15 mL) and 1M potassium tert-butoxide in THF (10 mL, 10 mmol). The yellow solution was allowed to stir and slowly warm to room temperature overnight. The reaction mixture was poured into water (75 mL) and extracted with ether (2×50 mL). The organic phase was washed with brine (50 mL), dried (Na2SO4), filtered and evaporated under vacuum to a yellow liquid, which was nearly pure by NMR and MS, and was used as such without further purification.
Reaction SMILES: [N+:1]([C:4]1[C:5]([NH:13][C@H:14]2[CH2:19][CH2:18][C@H:17]([CH2:20][OH:21])[CH2:16][CH2:15]2)=[C:6]2[S:12][CH:11]=[CH:10][C:7]2=[N:8][CH:9]=1)([O-:3])=[O:2].C(N(CC)C(C)C)(C)C.[CH3:31][S:32](Cl)(=[O:34])=[O:33]>C(Cl)Cl.O>[CH3:31][S:32]([O:21][CH2:20][C@H:17]1[CH2:16][CH2:15][C@H:14]([NH:13][C:5]2[C:4]([N+:1]([O-:3])=[O:2])=[CH:9][N:8]=[C:7]3[CH:10]=[CH:11][S:12][C:6]=23)[CH2:19][CH2:18]1)(=[O:34])=[O:33]
Reactant: O=[N+]([O-])c1cnc2ccsc2c1N[C@H]1CC[C@H](CO)CC1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: O
Product: CS(=O)(=O)OC[C@H]1CC[C@H](Nc2c([N+](=O)[O-])cnc3ccsc23)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a mixture of {trans-4-[(6-nitrothieno[3,2-b]pyridin-7-yl)amino]cyclohexyl}methanol (0.26 g, 0.84 mmol) and N,N-diisopropylethylamine (0.30 mL, 1.7 mmol) in methylene chloride (3 mL) was added methanesulfonyl chloride (0.085 mL, 1.1 mmol). The resulting mixture was stirred at room temperature for 2 h. After diluting with water, the mixture was extracted with dichloromethane. The organic layers were concentrated and purified on silica gel (eluting with 0 to 70% EtOAc in hexanes) to give the desired product (0.2 g, 61%). LCMS calculated for C15H20N3O5S2 (M+H)+: m/z=386.1. Found: 386.0.
Reaction SMILES: [NH:1]1[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1.[Br:10]N1C(=O)CCC1=O>O1CCCC1>[Br:10][C:3]1[C:4]2[C:5](=[N:6][CH:7]=[CH:8][CH:9]=2)[NH:1][CH:2]=1
Reactant: c1cnc2[nH]ccc2c1
Reactant: O=C1CCC(=O)N1Br
Solvent: C1CCOC1
Product: Brc1c[nH]c2ncccc12
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of 1H-pyrrolo[2,3-b]pyridine (15.6 g, 132 mmol) in 400 mL tetrahydrofuran at −40° C. was added a suspension of N-bromosuccinimide in 120 mL tetrahydrofuran. The reaction mixture was warmed to room temperature and allowed to stir for 4 hours. The solid was filtered off. The reaction mixture was quenched with a sodium metabisulfite solution, and extracted with ethyl acetate. The combined organics were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was triturated with 1:1 hexane/ethyl acetate and filtered. The filtrate was concentrated and the trituration step was repeated three more times to afford the title compound, which was used without further purification. MS (DCI+) m/z 196.9 (M+H)+.
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[C:19]([O:22][CH:23]1[C:24]([O:68][CH:69]([O:71][CH2:72][CH3:73])[CH3:70])([CH3:67])[CH2:25][CH2:26][CH:27]([O:59][Si](C(C)(C)C)(C)C)[CH2:28][C:29]([O:31][CH:32](/[C:37](/[CH3:58])=[CH:38]/[CH:39]=[CH:40]/[CH:41]([CH3:57])[CH2:42][CH:43]2[O:56][CH:44]2[CH:45]([CH3:55])[CH:46]([O:49][CH:50]([O:52][CH2:53][CH3:54])[CH3:51])[CH2:47][CH3:48])[CH:33]([CH3:36])[CH:34]=[CH:35]1)=[O:30])(=[O:21])[CH3:20]>O1CCCC1.C(OCC)(=O)C>[C:19]([O:22][CH:23]1[C:24]([O:68][CH:69]([O:71][CH2:72][CH3:73])[CH3:70])([CH3:67])[CH2:25][CH2:26][CH:27]([OH:59])[CH2:28][C:29]([O:31][CH:32](/[C:37](/[CH3:58])=[CH:38]/[CH:39]=[CH:40]/[CH:41]([CH3:57])[CH2:42][CH:43]2[O:56][CH:44]2[CH:45]([CH3:55])[CH:46]([O:49][CH:50]([O:52][CH2:53][CH3:54])[CH3:51])[CH2:47][CH3:48])[CH:33]([CH3:36])[CH:34]=[CH:35]1)=[O:30])(=[O:21])[CH3:20]
Reactant: CCOC(C)OC(CC)C(C)C1OC1CC(C)/C=C/C=C(\C)C1OC(=O)CC(O[Si](C)(C)C(C)(C)C)CCC(C)(OC(C)OCC)C(OC(C)=O)C=CC1C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: CCOC(C)OC(CC)C(C)C1OC1CC(C)/C=C/C=C(\C)C1OC(=O)CC(O)CCC(C)(OC(C)OCC)C(OC(C)=O)/C=C/C1C
Agent: CCOC(C)OC(CC)C(C)C1OC1CC(C)/C=C/C=C(\C)C1OC(=O)CC(O[Si](C)(C)C(C)(C)C)CCC(C)(OC(C)OCC)C(OC(C)=O)/C=C/C1C
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCOC(C)OC(CC)C(C)C1OC1CC(C)/C=C/C=C(\C)C1OC(=O)CC(O)CCC(C)(OC(C)OCC)C(OC(C)=O)C=CC1C
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A 1.0 M solution of tetrabutylammonium fluoride (0.026 mmol) in tetrahydrofuran (0.026 mL, 0.026 mmol) was added to a solution of (8E,12E,14E)-7-acetoxy-3-t-butyldimethylsiloxy-6,21-bis(1-ethoxyethoxy)-6,10,12,16,20-pentamethyl-18,19-epoxytricosa-8,12,14-trien-11-olide (19 mg, 0.024 mmol) in tetrahydrofuran (0.5 mL) at room temperature. The mixture was stirred at room temperature for 2 hours. Further, 0.026 mL of a 1.0 M solution of tetrabutylammonium fluoride in tetrahydrofuran (0.026 mL, 0.026 mmol) was added thereto at room temperature. After the reaction mixture was diluted with ethyl acetate, it was washed with brine, dried over anhydrous magnesium sulfate and evaporated. The resulting crude product was purified by silica gel column chromatography (Kanto silica gel 60N, spherical, neutral, 40 to 100 μm, eluate; hexane:ethyl acetate=70:30) to obtain the title compound (112 mg, 63%) as a colorless oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C@H:20]3[C@H:15]([CH2:16][CH2:17][CH2:18][CH2:19]3)[C:14](=[O:21])[NH:13][N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[C:22]1([CH:28]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)Cl)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.COC1C=C(C2[C@H]3[C@H](CCCC3)C(=O)N(C)N=2)C=CC=1OC>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C@H:20]3[C@H:15]([CH2:16][CH2:17][CH2:18][CH2:19]3)[C:14](=[O:21])[N:13]([CH:28]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: COc1ccc(C2=NNC(=O)[C@H]3CCCC[C@@H]23)cc1OC
Reactant: ClC(c1ccccc1)c1ccccc1
Agent: COc1ccc(C2=NN(C)C(=O)[C@H]3CCCC[C@@H]23)cc1OC
Product: COc1ccc(C2=NN(C(c3ccccc3)c3ccccc3)C(=O)[C@H]3CCCC[C@@H]23)cc1OC

Procedure:
Prepared from compound 1 and diphenylchloromethane as described for compound 8. Purified by chromatography (dichloromethane). Crystallized from methanol. M.p. 133°-135° C.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([OH:18])[CH2:16][Br:17])=[CH:11][C:10]=1[N+:19]([O-])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1COCC1>O=[Pt]=O.C1(C)C=CC=CC=1>[NH2:19][C:10]1[CH:11]=[C:12]([C@@H:15]([OH:18])[CH2:16][Br:17])[CH:13]=[CH:14][C:9]=1[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=[N+]([O-])c1cc([C@@H](O)CBr)ccc1OCc1ccccc1
Agent: O=[Pt]=O
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: Nc1cc([C@@H](O)CBr)ccc1OCc1ccccc1

Procedure:
(R)-1-[4-(benzyloxy)-3-nitrophenyl]-2-bromoethanol (0.200 g, 0.569 mmol) in 1:1 THF:toluene (5 mL) was reacted with 1% (w/w) PtO2 on a Parr shaker at 45 psi at rt overnight. The next morning the PtO2 was removed by filtration over celite. The product was concentrated to give the title compound. ES/MS calcd. for C15H17BrNO2+ 322.0. found m/z=322 (M+H)+.
Reaction SMILES: [CH:1]1([CH:6]([OH:10])[C:7]([OH:9])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.N[C@H](C([C:17]1([NH2:40])[C:23](=[O:24])[N:22]([CH2:25][C:26]([CH3:29])([CH3:28])[CH3:27])[C:21]2[CH:30]=[CH:31][CH:32]=[CH:33][C:20]=2[N:19]([CH2:34][C:35]([CH3:38])([CH3:37])[CH3:36])[C:18]1=[O:39])=O)C>>[CH:1]1([CH:6]([OH:10])[C:7]([NH:40][C@H:17]([C:23]([NH:40][CH:17]2[C:18](=[O:39])[N:19]([CH2:34][C:35]([CH3:38])([CH3:37])[CH3:36])[C:20]3[CH:33]=[CH:32][CH:31]=[CH:30][C:21]=3[N:22]([CH2:25][C:26]([CH3:28])([CH3:27])[CH3:29])[C:23]2=[O:24])=[O:24])[CH3:18])=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=C(O)C(O)C1CCCC1
Reactant: C[C@H](N)C(=O)C1(N)C(=O)N(CC(C)(C)C)c2ccccc2N(CC(C)(C)C)C1=O
Agent: Cl
Product: C[C@H](NC(=O)C(O)C1CCCC1)C(=O)NC1C(=O)N(CC(C)(C)C)c2ccccc2N(CC(C)(C)C)C1=O

Procedure:
Following General Procedure I above using cyclopentyl-α-hydroxyacetic acid (Example P) and 3-(L-alaninyl)-amino-2,4-dioxo-1,5-bis-(2,2-dimethylpropyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine hydrochloride (Example 8-V), the title compound was prepared as a white solid (melting point=119-129° C.). Purification was by flash chromatography eluting with CH2Cl2/EtOAc (1:1 gradient to 2:3). Rf=0.42 and 0.28 (CH2Cl2/EtOAc, 1:1).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.C(N(CC)CC)C.[O:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[C:23](Cl)=[O:24]>O1CCCC1>[O:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[C:23]([NH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2)=[O:24]
Reactant: O=C(Cl)c1ccco1
Reactant: Nc1ccc2[nH]ccc2c1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C(Nc1ccc2[nH]ccc2c1)c1ccco1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 50.4 %

Procedure:
To a solution of 2.09 gm (15.8 mMol) 5-amino-1H-indole in 20 mL tetrahydrofuran were added 2.6 mL (18.97 mMol) triethylamine and the solution was cooled in an ice bath. To the reaction mixture were then added dropwise 1.71 ml (17.4 mMol) 2-furoyl chloride. When this addition was complete the cooling bath was removed and the reaction mixture was stirred 1.5 hours at ambient temperature. At this point the reaction was diluted with water and extracted well with ethyl acetate. The organic solutions were combined and washed sequentially with water, 2N sodium hydroxide, water and saturated aqueous sodium chloride. The remaining organics were then dried over sodium sulfate and concentrated under reduced pressure to give a dark purple solid. The solid was subjected to flash chromatography, eluting with a gradient of dichloromethane containing 0-2% methanol. The recovered solid was crystallized from ethyl acetate to give 1.8 gm (50.3%) of 5-(2-furoyl)amino-1H-indole as pale purple crystals.
Reaction SMILES: C([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][CH2:13][CH:14]2[O:18][C:17](=[O:19])[NH:16][C:15]2=[O:20])=[CH:7][C:6]=1[O:21][CH3:22])(C)C.Cl>ClCCl.[Ti](Cl)(Cl)(Cl)Cl>[OH:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][CH2:13][CH:14]2[O:18][C:17](=[O:19])[NH:16][C:15]2=[O:20])=[CH:7][C:6]=1[O:21][CH3:22]
Reactant: COc1cc(CCCC2OC(=O)NC2=O)ccc1OC(C)C
Agent: Cl[Ti](Cl)(Cl)Cl
Agent: Cl
Solvent: ClCCl
Product: COc1cc(CCCC2OC(=O)NC2=O)ccc1O
Temperature: 0 °C
Reaction time: 1 h
Yield: 75.4 %

Procedure:
A solution of titanium tetrachloride (TiCl4) (10.6 g) in dichloromethane (10 ml) was added dropwise, at 0° C., to a solution of 5-[3-(4-isopropoxy-3-methoxy-phenyl)propyl]-2,4-oxazolidinedione (4.3 g) in dichloromethane (130 ml). The mixture was stirred for one hour at 0° C., which was poured into 2N HCl, followed by stirring for 15 minutes at room temperature. The organic layer was separated, and the aqueous layer was subjected to extraction with chloroform. The organic layers were combined, washed successively with water, 2N HCl and water, which was dried (MgSO4), followed by concentration to yield 5-[3-(4-hydroxy-3-methoxyphenyl)propyl]-2,4-oxazolidinedione (2.8 g, 76%). Recrystallization of the product from ethanol-hexane gave colorless prisms, m.p.147-148° C.
Reaction SMILES: C(O[C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])(C)(C)C.C(N(C(C)C)CC)(C)C.[CH3:23][C:24]1[C:28](C(Cl)=O)=[C:27]([CH3:32])[O:26][N:25]=1>C(Cl)Cl>[CH3:23][C:24]1[C:28]([C:6]([N:8]2[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]2)=[O:7])=[C:27]([CH3:32])[O:26][N:25]=1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: Cc1noc(C)c1C(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1noc(C)c1C(=O)N1CCNCC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A solution of 1-tert-butyloxycarbonyl-piperazine (4.581 mmol) and diisopropylethylamine (5.09 mmol) in methylene chloride (5 mL) was added to a 40 mL vial. 3,5-Dimethyl-isoxazole-4-carbonyl chloride (5.09 mmol) was added to the vial and the reaction was shaken overnight at room temperature. When the reaction was complete, it was diluted with methylene chloride (5 mL) and washed with 4 mL of 1 N hydrochloric acid followed by 4 mL of 10% potassium carbonate. The organic layer was concentrated in vacuo. The crude residue was dissolved in 5 mL of dioxane and 5 mL of 4M hydrochloric acid in dioxane. The reaction mixture was shaken overnight at room temperature then centrifuged. The supernatant was removed and the remaining solid was shaken with hexanes then centrifuged. The supernatant was removed, and the solids were collected and dried in vacuo to give (3,5-dimethyl-isoxazol-4-yl)-piperazin-1-yl-methanone. LR-MS: 210.2 [(M+H)+].
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][C:3]=1[C:4]([NH:6][NH2:7])=[O:5].[CH2:13]([O:31][C:32](Cl)=[O:33])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30].C(N(CC)CC)C.O>CC(N(C)C)=O>[CH2:13]([O:31][C:32]([N:6]([C:4](=[O:5])[C:3]1[CH:8]=[C:9]([OH:12])[CH:10]=[CH:11][C:2]=1[OH:1])[NH2:7])=[O:33])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30]
Reactant: CCCCCCCCCCCCCCCCCCOC(=O)Cl
Reactant: NNC(=O)c1cc(O)ccc1O
Solvent: CC(=O)N(C)C
Solvent: O
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCCCCCCCCOC(=O)N(N)C(=O)c1cc(O)ccc1O
Temperature: 40 °C

Procedure:
33.6 g of 2,5-dihydroxybenzoic acid hydrazide are dissolved in 150 ml of dimethylacetamide and 66.5 g of chloroformic acid octadecyl ester in 150 ml of dimethylacetamide, and 21 g of triethylamine, are added simultaneously over the course of 30 minutes. Thereafter the reaction mixture is warmed to 40° C for 3 hours whilst stirring, cooled and poured into 2 litres of water. The N-(2,5-dihydroxybenzoyl)-hydrazinecarboxylic acid octadecyl ester obtained (Stabiliser No. 8) forms a pulverulent precipitate which is isolated, washed with water, dried at 80° C and recrystallised from isopropanol. Melting point 163° C.
Reaction SMILES: O.Cl.[F:3][C:4]1[CH:9]=[C:8]([N+:10]([O-])=O)[CH:7]=[CH:6][C:5]=1[N:13]1[CH2:18][CH2:17][O:16][CH2:15][C:14]1=[O:19].C([O-])(O)=O.[Na+]>CO.[Fe]>[NH2:10][C:8]1[CH:7]=[CH:6][C:5]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][C:14]2=[O:19])=[C:4]([F:3])[CH:9]=1
Reactant: O=C1COCCN1c1ccc([N+](=O)[O-])cc1F
Agent: [Fe]
Agent: Cl
Agent: O=C([O-])O
Solvent: O
Solvent: CO
Product: Nc1ccc(N2CCOCC2=O)c(F)c1
Temperature: 65 °C
Reaction time: 0.33 h
Yield: 56.9 %

Procedure:
A mixture of iron powder (8.8 g, 158 mmol), water (60 mL) and hydrochloric acid (2 mL) was stirred at 65° C. for 20 min. It was then cooled to rt and the aqenous layer was poured out. A solution of 4-(2-fluoro-4-nitrophenyl)morpholin-3-one (3.8 g, 15.8 mmol) in MeOH (100 mL) was added and the resuting mixture was acidified to pH 2 with hydrochloric acid and stirred at 65° C. for 4 h. The mixture was cooled to rt, adjusted to pH 8 with saturated NaHCO3 aqueous solution and filtered. The MeOH was removed in vacuo and the mixture was extracted with EtOAc (20 mL×3). The combined organic layers were washed with brine (20 mL×4), dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by a silica gel column chromatography (PE/EtOAc (V/V)=1:2) to give the title compound as a white solid (1.89 g, 57%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7](=[O:11])[CH2:8][CH2:9][CH3:10])[CH:2]=1.[Br:12]Br.S([O-])([O-])(=O)=S.[Na+].[Na+].C(=O)([O-])[O-].[K+].[K+]>Br.C(O)(=O)C>[Br:12][CH:8]([CH2:9][CH3:10])[C:7]([C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1)=[O:11]
Reactant: CCCC(=O)c1cccnc1
Reactant: BrBr
Agent: Br
Agent: O=C([O-])[O-]
Agent: O=S([O-])([O-])=S
Solvent: CC(=O)O
Product: CCC(Br)C(=O)c1cccnc1
Temperature: 60 °C
Reaction time: 0.5 h

Procedure:
To a solution of 1-(3-pyridyl)-1-butanone (20.0 g) in 47% aqueous hydrobromic acid (40 ml) and acetic acid (40 ml) was added bromine (15.2 ml), and the mixture was stirred at 60° C. for 30 minutes. The reaction mixture was poured into ice-water, and after adding a saturated aqueous sodium thiosulfate solution, potassium carbonate was added to the mixture to adjust pH to 4. The reaction mixture was extracted with ethyl acetate, washed successively with a saturated aqueous sodium hydrogen carbonate solution and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to obtain a crude product of 2-bromo-1-(3-pyridyl)-1-butanone (30.15 g) as brownish oil.
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH2:11][C:10]2([CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:13]2=O)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:26]1(C)C=CC=CC=1>N1C=CC=CC=1.C1([Ti](C2C=CC=C2)(C)C)C=CC=C1>[CH2:1]([N:8]1[CH2:12][CH2:11][C:10]2([CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:13]2=[CH2:26])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)OC(=O)N1CCCC2(CCN(Cc3ccccc3)C2)C1=O
Reactant: Cc1ccccc1
Agent: C[Ti](C)(C1C=CC=C1)C1C=CC=C1
Solvent: c1ccncc1
Product: C=C1N(C(=O)OC(C)(C)C)CCCC12CCN(Cc1ccccc1)C2
Temperature: 70 °C

Procedure:
8.7 mmol of tert-butyl 2-benzyl-6-oxo-2,7-diazaspiro[4.5]decane-7-carboxylate are dissolved in a mixture of 75 ml of toluene and 0.75 ml of pyridine. The solution is admixed with 10.0 mmol of bis(cyclopentadienyl)dimethyltitanium [1271-66-5] and heated at 70° C. for 20 hours. The reaction solution is evaporated and the residue is taken up in pentane. The mixture is filtered over Hyflo and the filtrate is evaporated. From the residue the title compound is identified by means of flash chromatography (SiO2 60 F) on the basis of the Rf value.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.C[O-].[Na+]>C(O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Cl-].[Ru+2]>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:10])[CH3:9])=[CH:4][CH:3]=1
Reactant: CC(=O)c1ccc(Br)cc1
Agent: [Ru+2]
Agent: C[O-]
Agent: [Cl-]
Solvent: CCO
Product: CC(O)c1ccc(Br)cc1
Temperature: 80 °C
Reaction time: 1 h

Procedure:
Tris(triphenylphosphine)ruthenium(II) chloride (3.8 mg, 4 μmol, 1 mol %) and a chiral ligand (M=Ru, R=n-Pr, Ar=C6H5—, 2.6 μmol, 0.65 mol %) were dissolved in ethanol (3 mL) under nitrogen atmosphere, and then heated and stirred for 1 h at 80° C. After the mixture was cooled to room temperature, p-bromoacetophenone (0.4 mmol), ethanol (2 mL) and a solution of sodium methoxide in ethanol (0.8 mL, 0.2 M) were added thereto. Thereafter, the reaction system was placed in an autoclave, and stirred for 12 h under H2 (10 atm) at 25° C. The solvent was removed under reduced pressure, and the resultants were separated by column chromatography (silica gel column; eluent:ethyl acetate/petroleum ether=1/5). Accordingly, pure 1-(p-bromophenyl)ethanol was obtained and the ee value (ee=97%) was measured by GC analysis.