Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[CH:4][C:3]=1[N:11]1[C:15](=[O:16])[N:14]([CH2:17][CH2:18][CH2:19][F:20])[N:13]=[N:12]1>C(O)(=O)C.O.[Fe]>[NH2:8][C:6]1[CH:5]=[CH:4][C:3]([N:11]2[C:15](=[O:16])[N:14]([CH2:17][CH2:18][CH2:19][F:20])[N:13]=[N:12]2)=[C:2]([F:1])[CH:7]=1
Reactant: O=c1n(CCCF)nnn1-c1ccc([N+](=O)[O-])cc1F
Agent: [Fe]
Solvent: O
Solvent: CC(=O)O
Product: Nc1ccc(-n2nnn(CCCF)c2=O)c(F)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 50.6 %

Procedure:
To a stirred solution of 15.0 g (0.096 mole) of 1-(2-fluoro-4-nitrophenyl)-4-(3-fluoropropyl)-1,4-dihydro-5H-tetrazol-5-one in 200 mL of glacial acetic acid and 10 mL of water, heated at 45° C., was added portionwise 15.0 g (0.27 mole) of iron powder. The reaction mixture was allowed to cool to room temperature and stir for approximately two hours. This mixture was filtered through a pad of Celite filter aid. The filtrate was diluted with 200 mL of water, and the resultant mixture was extracted with diethyl ether. The organic extract was dried over anhydrous magnesium sulfate and was filtered. The filtrate was evaporated under reduced pressure leaving an oil. This oil was purified by column chromatography on silica gel, eluting with methylene chloride, to yield 12.4 g of 1-(4-amino-2-fluorophenyl)-4-(3-fluoropropyl)-1,4-dihydro-5H- tetrazol-5-one as an oil.
Reaction SMILES: [Si]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([C:36]1[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:37]=1[F:43])([CH2:24][CH2:25][CH2:26][CH2:27][O:28][Si](C(C)(C)C)(C)C)[S:14]([C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)(=[O:16])=[O:15])(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)C>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([S:14]([C:13]([C:36]2[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:37]=2[F:43])([CH2:12][CH2:11][CH2:10][CH2:9][OH:8])[CH2:24][CH2:25][CH2:26][CH2:27][OH:28])(=[O:16])=[O:15])=[CH:18][CH:19]=1
Reactant: CC(C)(C)[Si](C)(C)OCCCCC(CCCCO[Si](C)(C)C(C)(C)C)(c1cc(F)ccc1F)S(=O)(=O)c1ccc(Cl)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOCC
Product: O=S(=O)(c1ccc(Cl)cc1)C(CCCCO)(CCCCO)c1cc(F)ccc1F
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a solution of 2-[5-(t-butyldimethylsilyloxy)-1-[4-(t-butyldimethylsilyloxy)butyl]-1-(4-chlorophenylsulfonyl)pentyl]-1,4-difluorobenzene (158 mg, 0.234 mmol) in tetrahydrofuran (4 ml) was added tetrabutylammonium fluoride (a 1M tetrahydrofuran solution, 0.702 ml, 0.702 mmol). The resulting mixture was stirred at room temperature for 24 hours. After concentration of the reaction mixture, the residue was dissolved in diethyl ether, followed by successive washing with water and brine, drying over MgSO4, and concentration. The residue thus obtained was purified by medium-pressure chromatography on a silica gel column (5% methanol-methylene chloride) to yield a colorless solid. The resulting solid was recrystallized from ethyl acetate-hexane, whereby the title compound (97.0 mg, 93%) was obtained as a colorless solid.
Reaction SMILES: N(OC(C)(C)C)=O.N[C:9]1[N:13]([C:14]2[C:19]([Cl:20])=[CH:18][C:17]([C:21]([F:24])([F:23])[F:22])=[CH:16][C:15]=2[Cl:25])[N:12]=[C:11]([C:26]#[N:27])[C:10]=1[C:28](=[O:33])[C:29]([F:32])([F:31])[F:30].CCCCCC.ClCCl>O1CCCC1>[C:26]([C:11]1[C:10]([C:28](=[O:33])[C:29]([F:30])([F:31])[F:32])=[CH:9][N:13]([C:14]2[C:19]([Cl:20])=[CH:18][C:17]([C:21]([F:24])([F:22])[F:23])=[CH:16][C:15]=2[Cl:25])[N:12]=1)#[N:27]
Reactant: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1C(=O)C(F)(F)F
Agent: CC(C)(C)ON=O
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: ClCCl
Product: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)cc1C(=O)C(F)(F)F
Temperature: 55 °C
Reaction time: 16 h

Procedure:
t-Butyl nitrite (12.45 ml) was added dropwise to a stirred solution of 5- amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoroacetylpyrazole (JP-A-8-311036; 30 g) in tetrahydrofuran (250 ml) and the mixture stirred at 55° C. for 16 hours. Further quantities of t-butyl nitrite added/subsequent periods of stirring at 55° C. were as follows: 9 ml/7 hours, 6 ml/16 hours, 9 ml/6 hours, 4.75 ml/16 hours, 6 ml/6 hours and 3.5 ml/22 hours. The reaction mixture was allowed to cool and evaporated under reduced pressure, then the residue combined with those obtained from three identical preparations. Purification by column chromatography on silica gel (1 Kg), using hexane:dichloromethane (6:4) and then dichloromethane as eluants, gave a yellow oil which, on trituration with hexane (3×50 ml) followed by dichloromethane (100 ml), provided the title compound as a white solid, m.p. 124-125° C. δ(CDCl3): 7.83 (s,2H), 8.30 (s,1H). MS (thermospray): M/Z [M+H] 401.7; C13H3Cl2F6N3O+H requires 401.96.
Reaction SMILES: [C:1]([O:5][C:6](=[O:16])[N:7]([C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][N:10]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[B:22]([O:31][CH:32]([CH3:34])[CH3:33])([O:27][CH:28]([CH3:30])[CH3:29])OC(C)C.OCC(C)(CO)C>C1COCC1>[C:1]([O:5][C:6](=[O:16])[N:7]([CH3:8])[C:9]1[CH:14]=[CH:13][C:12]([B:22]2[O:27][C:28]([CH3:29])([CH3:30])[C:32]([CH3:33])([CH3:34])[O:31]2)=[CH:11][N:10]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)OB(OC(C)C)OC(C)C
Reactant: CN(C(=O)OC(C)(C)C)c1ccc(Br)cn1
Agent: CC(C)(CO)CO
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CN(C(=O)OC(C)(C)C)c1ccc(B2OC(C)(C)C(C)(C)O2)cn1
Temperature: -78 °C
Reaction time: 0.33 h

Procedure:
To a solution of (5-bromo-pyridin-2-yl)-methyl-carbamic acid tert-butyl ester (3.286 g) in THF (50 mL) at −78° C. was added n-butyllithium (5.15 mL of a 2.5 M solution in hexanes). After stirring at −78° C. for 20 min, triisopropyl borate (5.31 mL) was added. The reaction was warmed to −45° C. over 4 h, then, neopentyl glycol (1.19 g) was added. The reaction was warmed to room temperature over 16 h and then quenched with ice/water (70 mL) and extracted into dichloromethane (3×40 mL). The organic layers were dried (MgSO4), reduced in vacuo and purified on silica to give methyl-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-2-yl]-carbamic acid tert-butyl ester as an off-white solid.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:14]3[C:15]([CH3:20])=[N:16][O:17][C:18]=3[CH3:19])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[N+:21]([O-])=O.[N:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C@H:30]([NH2:32])[CH3:31]>C(#N)C>[CH3:20][C:15]1[C:14]([C:8]2[CH:7]=[C:6]3[C:11]([C:2]([NH:32][C@@H:30]([C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][N:24]=4)[CH3:31])=[C:3]([NH2:21])[CH:4]=[N:5]3)=[CH:10][C:9]=2[O:12][CH3:13])=[C:18]([CH3:19])[O:17][N:16]=1
Reactant: COc1cc2c(Cl)c([N+](=O)[O-])cnc2cc1-c1c(C)noc1C
Reactant: C[C@@H](N)c1ccccn1
Solvent: CC#N
Product: COc1cc2c(N[C@H](C)c3ccccn3)c(N)cnc2cc1-c1c(C)noc1C
Temperature: 40 °C
Reaction time: 1 h

Procedure:
A solution of 4-chloro-7-(3,5-dimethyl-4-isoxazolyl)-6-(methoxy)-3-nitroquinoline (for a preparation see Intermediate 18, 400 mg,) and (R)-1-(pyridin-2-yl)ethanamine (293 mg) in acetonitrile (30 ml) was heated at 60° C. for 2 h. The reaction mixture was extracted with DCM and washed with a saturated solution of sodium hydrogen carbonate. The organic was dried over Na2SO4, filtered and concentrated to dryness. The resulting compound was taken-up in ether, filtered and dried in vacuo. The residue was dissolved in ethanol (20 ml) and HCl (3.8 ml). Tin (II) chloride dihydrate (0.89 g) was then added in four portions and the reaction mixture was stirred for 1 h at 40° C. The reaction mixture was hydrolysed using a solution of sodium hydroxide (1N). The mixture was extracted with DCM, the organic dried over Na2SO4, filtered over Celite and concentrated to dryness. The crude product was purified via flash column chromatography on silica gel eluting with DCM/MeOH (95/5) and the obtained product was taken-up in diisopropylether to give 7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-N4-[(1R)-1-(2-pyridinyl)ethyl]-3,4-quinolinediamine (250 mg) as a brown powder. LC/MS: Rt 2.62 min.
Reaction SMILES: [N:1]#[C:2][NH2:3].CC(C)([O-])C.[K+].[CH3:10][C:11]([C:14]1[CH:15]=[C:16]([CH:25]=[C:26]2[O:30][C:29](SC)=[N:28][C:27]2=[O:33])[CH:17]=[C:18]([C:21]([CH3:24])([CH3:23])[CH3:22])[C:19]=1[OH:20])([CH3:13])[CH3:12]>C(O)C>[CH3:10][C:11]([C:14]1[CH:15]=[C:16]([CH:25]=[C:26]2[O:30][C:29]([NH:3][C:2]#[N:1])=[N:28][C:27]2=[O:33])[CH:17]=[C:18]([C:21]([CH3:24])([CH3:23])[CH3:22])[C:19]=1[OH:20])([CH3:13])[CH3:12]
Reactant: CSC1=NC(=O)C(=Cc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)O1
Reactant: N#CN
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCO
Product: CC(C)(C)c1cc(C=C2OC(NC#N)=NC2=O)cc(C(C)(C)C)c1O
Reaction time: 0.25 h
Yield: 38 %

Procedure:
A suspension of 0.38 g (0.0090 mole) of cyanamide in 50 mL of ethanol is cooled in ice and treated in small portions with 0.93 g (0.0083 mole) of potassium tert-butoxide. After stirring for 15 minutes, 2.6 g (0.0075 mole) of 5-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenylmethylene]-2-(methylthio)-4(5H)-oxazolone is added, followed by an additional 25 mL of ethanol. The mixture is stirred at reflux for 3 hours, then cooled to allow precipitation of the potassium salt of the product. The salt is filtered, washed several times with ether, suspended in 100 mL of cold water, and acidified with 1.0 mL of acetic acid. The mixture is stirred for 30 minutes and extracted with ethyl acetate (4×75 mL). The combined organic layers are washed with brine (2×150 mL), dried (anhydrous sodium sulfate), and evaporated to yield 1.0 g (38%) of the nitrile product, [5-[[3,5-bis(1,1-dimethylethyl)- 4-hydroxyphenyl]methylene]-4,5-dihydro-4-oxo-2-oxazolyl]cyanamide. A sample recrystallized from hexane:ethyl acetate had mp 220° C. dec.
Reaction SMILES: [H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][CH:13]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:12](=[O:21])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH3:22][C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=1)[CH2:26]Br>CN(C)C=O>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C:13]([CH2:22][C:23]2[CH:30]=[CH:29][CH:28]=[C:25]([CH3:26])[CH:24]=2)([C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:12](=[O:21])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]
Reactant: CCOC(=O)C1CCN(C(=O)OC(C)(C)C)CC1=O
Reactant: Cc1cccc(CBr)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)C1(Cc2cccc(C)c2)CCN(C(=O)OC(C)(C)C)CC1=O
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a cold (0° C.) slurry of sodium hydride (0.29 g, 12 mmol) in anhydrous dimethylformamide (50 mL), a solution of ethyl N-tert-butoxycarbonyl-3-oxo-piperidine-4-carboxylate (2.73 g, 10 mmol) in DMF (10 mL) was added. The mixture was stirred at 0° C. for 30 min., and at room temp. for 30 min. The resultant solution was cooled back to 0° C. and treated with 3-methylbenzyl bromide (1.63 mL, 12 mmol). The reaction mixture was stirred at room temp. overnight and concentrated under vacuum. The residue was partitioned between ethyl acetate and aqueous sodium bicarbonate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 17.5% ethyl acetate in hexane. Collection and concentration of appropriate fractions provided the title compound.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][C:4]1([CH2:10][CH2:11]Cl)[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1.Cl.[Cl:14]CCC1CCCCC1>>[Cl:1][CH2:2][CH2:3][C:4]1([CH:10]([Cl:14])[CH3:11])[CH2:9][CH2:8][CH2:7][CH2:6][CH2:5]1
Reactant: ClCCC1(CCCl)CCCCC1
Reactant: ClCCC1CCCCC1
Agent: Cl
Product: CC(Cl)C1(CCCl)CCCCC1

Procedure:
In this example 100.0 grams of cyclohexane, 17.0 grams of vinyl chloride, 6.0 grams of di-t-butyl peroxide and 21.0 grams of concentrated 37% hydrochloric acid in 21.0 grams of water were added to an 850 ml rotating autoclave. The rotating autoclave was heated to a temperature of between 130° and 140° C. at an initial pressure of 30 atmospheres of nitrogen for a period of time comprising 4 hours. At the end of this time, heating was terminated thereby allowing the autoclave to return to room temperature, and the autoclave was vented. The product was recovered and distilled. The material boiling higher than the unreacted cyclohexane was analyzed by means of preparatory gas-liquid chromatography and infrared spectroscopy. The major product showed infrared absorption at 2860 cm-1 and 2930 cm-1, thereby indicating the presence of a cyclohexyl ring and at 660 cm-1 and 730 cm-1, thereby indicating the presence of a primary alkyl chloride. It should be noted that the infrared analysis failed to disclose an absorption at 1375 cm-1, thereby indicating an absence of methyl grouping. It was determined as a direct conclusion from the infrared analysis that the product (2-chloroethyl)cyclohexane was produced in 30 mole percent yield. The product obtained in lower yield showed infrared absorption at 2860 cm-1 and 2940 cm-1, thereby indicating the presence of a cyclohexyl grouping, at 450 cm-1, thereby indicating the presence of a CH2 bonding and at 615 cm-1 and 670 cm-1, thereby indicating the presence of a secondary alkyl chloride. It was determined by mass spectroscopy that the largest significant ion found had a molecular weight of 172-174 atomic mass units. It may be concluded from the above infrared and mass spectroscopy data that the product was x-(1-chloroethyl)-y-(2-chloroethyl)cyclohexane which eliminated hydrogen chloride (loss of chlorine attached to the secondary carbon atom) during the mass spectroscopy analysis to form x-vinyl-y-(2-chloroethyl)cyclohexane, the molecular weight of which is 172.8 atomic mass units, in 17 mole percentage yield. It seems probable that bis-(2-chloroethyl)cyclohexane loses hydrogen chloride more readily than does (2-chloroethyl)cyclohexane. In the presence of hydrogen chloride the resulting vinyl compound adds hydrogen chloride to form a (2-chloroethyl)-(1-chloroethyl)cyclohexane. In the absence of hydrogen chloride, the vinyl compound polymerizes.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:27])[C@H:4]([CH2:16][N:17]1[CH:21]=[CH:20][N:19]=[C:18]1[N:22]=[CH:23][N:24]([CH3:26])[CH3:25])[NH:5]C(OCC1C=CC=CC=1)=O.O>CO.[Pd]>[CH3:1][O:2][C:3](=[O:27])[C@H:4]([CH2:16][N:17]1[CH:21]=[CH:20][N:19]=[C:18]1[N:22]=[CH:23][N:24]([CH3:26])[CH3:25])[NH2:5]
Reactant: COC(=O)[C@H](Cn1ccnc1N=CN(C)C)NC(=O)OCc1ccccc1
Agent: [Pd]
Solvent: CO
Solvent: O
Product: COC(=O)[C@@H](N)Cn1ccnc1N=CN(C)C
Reaction time: 2 h
Yield: 80.3 %

Procedure:
3- (2-Dimethylaminomethyleneaminoimidazol-1-yl)-N-(benzyloxycarbonyl)-L-alanine methyl ester (937 mg) was dissolved in methanol (25 ml), and 50% water-containing 10% Pd/C (468 mg) was added. Then, the mixture was vigorously stirred for 2 hours under an atmosphere of hydrogen. The catalyst was filtered off. The solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel flush column chromatography (eluent: 7% ammonia-containing ethanol-chloroform a 3:97) to give the title compound (482 mg).
Reaction SMILES: [CH:1]([N:4]([CH:16]([CH3:18])[CH3:17])[CH2:5][CH2:6][NH:7][C:8]1[N:13]=[C:12]([CH3:14])[CH:11]=[C:10]([CH3:15])[N:9]=1)([CH3:3])[CH3:2].[H-].[Na+].[CH3:21][N:22]([CH3:26])[C:23](Cl)=[O:24].[OH-].[Na+]>C(O)C.C1(C)C=CC=CC=1>[CH3:21][N:22]([CH3:26])[C:23]([N:7]([CH2:6][CH2:5][N:4]([CH:1]([CH3:2])[CH3:3])[CH:16]([CH3:18])[CH3:17])[C:8]1[N:9]=[C:10]([CH3:15])[CH:11]=[C:12]([CH3:14])[N:13]=1)=[O:24]
Reactant: Cc1cc(C)nc(NCCN(C(C)C)C(C)C)n1
Reactant: CN(C)C(=O)Cl
Agent: [H-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: Cc1ccccc1
Product: Cc1cc(C)nc(N(CCN(C(C)C)C(C)C)C(=O)N(C)C)n1

Procedure:
A mixture of 2-(2-diisopropylaminoethylamino)-4,6-dimethyl pyrimidine (17.0 g. 0.068 mole) and sodium hydride (50% in mineral oil) (4.19 g., 0.86 mole) in 175 ml. of dry toluene is stirred under nitrogen at 85°-95° C. for one half hour and then heated under reflux for one half hour. Dimethylcarbamoyl chloride (8.6 g., 0.08 mole) is added and heating under reflux is continued for twenty-four hours. The reaction is cooled and ethanol (10 ml) and sodium hydroxide (75 ml., 3.3 N) are added. The aqueous layer is extracted with methylene chloride and the extracts are dried over sodium sulfate and concentrated to an oil. The oil is distilled at 0.5 mm of Hg and the product boiling at 155°-158° C. is collected.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:30])=[C:6]([C:8]([CH3:29])([CH3:28])[CH2:9][C:10]([OH:27])([C:23]([F:26])([F:25])[F:24])[CH2:11][NH:12][C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[C:18](=[O:19])[O:17][CH2:16]3)[CH:7]=1.[Br:31]N1C(=O)CCC1=O>CN(C)C=O.C(OCC)(=O)C>[Br:31][C:14]1[C:13]([NH:12][CH2:11][C:10]([OH:27])([C:23]([F:24])([F:26])[F:25])[CH2:9][C:8]([C:6]2[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[OH:30])([CH3:28])[CH3:29])=[CH:22][CH:21]=[C:20]2[C:15]=1[CH2:16][O:17][C:18]2=[O:19]
Reactant: CC(C)(CC(O)(CNc1ccc2c(c1)COC2=O)C(F)(F)F)c1cc(F)ccc1O
Reactant: O=C1CCC(=O)N1Br
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)(CC(O)(CNc1ccc2c(c1Br)COC2=O)C(F)(F)F)c1cc(F)ccc1O

Procedure:
55 mg of (−)-5-[4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-pentylamino]-phthalide is mixed under nitrogen in 1 ml of dimethylformamide at 2° C. with 18 mg of N-bromosuccinimide. After 2 hours at this temperature, it is diluted with 20 ml of ethyl acetate, extracted with water, and the organic phase is dried (Na2SO4) and concentrated by evaporation. With chromatography on silica gel, the title compound in crystalline form is eluted with hexane/ethyl acetate (4:1), flash point 228-232° C.
Reaction SMILES: [C:1]([C:9]1[CH:10]=[C:11]([CH:20]=[C:21]([C:24]([CH2:27]C(C)(C)C)([CH3:26])[CH3:25])[C:22]=1[OH:23])[CH2:12][P:13]1(=[O:19])[O:18]CC[CH2:15][O:14]1)([CH2:4]C(C)(C)C)([CH3:3])[CH3:2].[CH3:32][C:33](C)([CH2:36]O)[CH2:34]O.C(C1C=C(C=C(C(CC(C)(C)C)(C)C)C=1O)CP(=O)(OC1C=CC=CC=1)OC1C=CC=CC=1)(CC(C)(C)C)(C)C.C(C1C=C(C=C(C(C)(C)C)C=1O)CP(=O)(OC1C=CC=CC=1)OC1C=CC=CC=1)(C)(C)C>>[C:1]([C:9]1[CH:10]=[C:11]([CH:20]=[C:21]([C:24]([CH3:27])([CH3:26])[CH3:25])[C:22]=1[OH:23])[CH2:12][P:13]1(=[O:19])[O:18][CH2:32][C:33]([CH3:36])([CH3:34])[CH2:15][O:14]1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)CC(C)(C)c1cc(CP2(=O)OCCCO2)cc(C(C)(C)CC(C)(C)C)c1O
Reactant: CC(C)(CO)CO
Agent: CC(C)(C)CC(C)(C)c1cc(CP(=O)(Oc2ccccc2)Oc2ccccc2)cc(C(C)(C)CC(C)(C)C)c1O
Agent: CC(C)(C)c1cc(CP(=O)(Oc2ccccc2)Oc2ccccc2)cc(C(C)(C)C)c1O
Product: CC1(C)COP(=O)(Cc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)OC1

Procedure:
Similarly, 1-(3,5-di-tert-octyl-4-hydroxybenzyl)-1-oxo-2,6-dioxa-1-phosphacyclohexane is made by substituting 1,3-propanediol for 2,2-dimethyl-1,3-propanediol and diphenyl 3,5-di-tert-octyl-4-hydroxybenzylphosphonate for diphenyl 3,5-di-tert-butyl-4-hydroxybenzylphosphonate in the above example.
Reaction SMILES: [CH2:1]([C:3]1[O:4][C:5]([C:8]([O-:10])=[O:9])=[CH:6][N:7]=1)[CH3:2].[OH-].[Na+]>CO>[CH2:1]([C:3]1[O:4][C:5]([C:8]([OH:10])=[O:9])=[CH:6][N:7]=1)[CH3:2]
Reactant: CCc1ncc(C(=O)[O-])o1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCc1ncc(C(=O)O)o1
Temperature: 25 °C
Reaction time: 18 h
Yield: 61.5 %

Procedure:
To a solution of 2-ethyloxazole-5-carboxylate (470 mg, 2.81 mmol) in MeOH (10 mL) is added 1N NaOH (6 mL, 6 mmol). After stirring at room temperature for 18 hours, the crude is concentrated under reduced pressure to remove MeOH and is diluted with EtOAc. The organic layer is washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to give 2-ethyloxazole-5-carboxylic acid (244 mg). 1H NMR (400 MHz, CD3OD) δ ppm 1.36 (t, J=7.7 Hz, 3 H) 2.89 (q, J=7.6 Hz, 2 H) 5.15 (br. s., 1 H) 7.69 (s, 1 H)
Reaction SMILES: C([Li])CCC.C(NC(C)C)(C)C.[Cl:13][C:14]1[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=1.[CH2:20]([C:22]1[CH:29]=[CH:28][C:25]([CH:26]=[O:27])=[CH:24][CH:23]=1)[CH3:21].[Cl-].[NH4+]>C1COCC1.CCCCCC>[Cl:13][C:14]1[CH:19]=[CH:18][N:17]=[CH:16][C:15]=1[CH:26]([C:25]1[CH:28]=[CH:29][C:22]([CH2:20][CH3:21])=[CH:23][CH:24]=1)[OH:27]
Reactant: CCc1ccc(C=O)cc1
Reactant: Clc1ccncc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CC(C)NC(C)C
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCc1ccc(C(O)c2cnccc2Cl)cc1
Temperature: -78 °C
Reaction time: 0.42 h
Yield: 71.2 %

Procedure:
A 1.58 M n-hexane solution of n-butyllithium (30.1 mL, 0.0476 mol) and THF (125 mL) were mixed and a solution of diisopropylamine (6.67 mL, 0.0476 mol) in THF (25 mL) was added dropwise thereto at −20° C., followed by stirring for 25 minutes. After cooling the reaction mixture to −78° C., a solution of 4-chloropyridine (5.4 g, 0.0476 mol) in THF (25 mL) was added dropwise. After 15 minutes, a solution of 4-ethylbenzaldehyde (6.4 g, 0.0477 mol) in THF (25 mL) was added dropwise and stirred for 30 minutes. After warming the reaction mixture to room temperature, saturated aqueous ammonium chloride was added and the resulting mixture was then extracted twice with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate. After the solvent was distilled off under reduced pressure, the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to give (4-chloropyridin-3-yl)-(4-ethylphenyl)methanol (8.4 g, 71%) as a light-yellow crystal.
Reaction SMILES: C(OC([N:11]1[C@H:15]([C:16]([N:18]2[CH2:23][CH2:22][N:21]([C:24]3[CH:29]=[C:28]([CH3:30])[CH:27]=[CH:26][C:25]=3[CH3:31])[CH2:20][CH2:19]2)=[O:17])[CH2:14][N:13]([S:32]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)(=[O:34])=[O:33])[C:12]1=[O:41])=O)C1C=CC=CC=1>C(OCC)(=O)C.[Pd]>[C:35]1([S:32]([N:13]2[CH2:14][C@@H:15]([C:16]([N:18]3[CH2:19][CH2:20][N:21]([C:24]4[CH:29]=[C:28]([CH3:30])[CH:27]=[CH:26][C:25]=4[CH3:31])[CH2:22][CH2:23]3)=[O:17])[NH:11][C:12]2=[O:41])(=[O:34])=[O:33])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1
Reactant: Cc1ccc(C)c(N2CCN(C(=O)[C@@H]3CN(S(=O)(=O)c4ccccc4)C(=O)N3C(=O)OCc3ccccc3)CC2)c1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: Cc1ccc(C)c(N2CCN(C(=O)[C@@H]3CN(S(=O)(=O)c4ccccc4)C(=O)N3)CC2)c1
Yield: 52.1 %

Procedure:
(S)-3-Benzenesulfonyl-5-[4-(2,5-dimethyl-phenyl)-piperazine-1-carbonyl]-2-oxo-imidazolidine-1-carboxylic acid benzyl ester (300 mg) in ethyl acetate (3 mL) were hydrogenated in the presence of 10% Pd/C (28 mg). After removal of the catalyst and evaporation of the solvent, the residue was purified by column chromatography (SiO2, ethyl acetate) to yield (S)-1-benzenesulfonyl-4-[4-(2,5-dimethyl-phenyl)-piperazine-1-carbonyl]-imidazolidin-2-one (120 mg) as a white solid. MS: 443.4 ([M+H]+)
Reaction SMILES: [O:1]1[CH:5]=[C:4]([C:6]2[CH:11]=[CH:10][C:9]([C:12](=[O:14])[CH3:13])=[CH:8][CH:7]=2)[N:3]=[CH:2]1.[F:15][C:16]([F:23])([F:22])[C:17](OCC)=[O:18].C[O-].[Na+].Cl>C(OC)(C)(C)C>[F:15][C:16]([F:23])([F:22])[C:17](=[O:18])[CH2:13][C:12]([C:9]1[CH:8]=[CH:7][C:6]([C:4]2[N:3]=[CH:2][O:1][CH:5]=2)=[CH:11][CH:10]=1)=[O:14]
Reactant: CCOC(=O)C(F)(F)F
Reactant: CC(=O)c1ccc(-c2cocn2)cc1
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: COC(C)(C)C
Product: O=C(CC(=O)C(F)(F)F)c1ccc(-c2cocn2)cc1
Reaction time: 20 h
Yield: 99 %

Procedure:
To a stirred solution of 1-[4-(1,3-oxazol-4-yl)phenyl]-1-ethanone (256 mg, 1.37 mmol), ethyl trifluoroacetate (214 mg, 1.51 mmol) in t-butylmethylether (22 ml) was added sodium methoxide (28 wt. % solution in methanol; 0.4 ml, 1.67 mmol) over 5 minutes, and the mixture was stirred for 20 hours. The mixture was made neutral by addition of 2N HCl, and the whole was extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was used for next reaction without further purification. (433 mg, 99% yield).