Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:6](C(F)(F)F)=[CH:5][C:4](Cl)=[C:3]([O:12][C:13]2[CH:14]=[CH:15][C:16]([N+]([O-])=O)=[C:17](C(O)=O)[CH:18]=2)[CH:2]=1.C1C(C(F)(F)F)=CC(Cl)=C(OC2C=CC([N+]([O-])=O)=C(C([O-])=O)C=2)C=1.[Na+].CCOC1C=C(OC2C=CC(C(F)(F)F)=CC=2Cl)C=CC=1[N+]([O-])=O.O1C=CN=N1.CC(OC1C=C(N2N=C(C(C)(C)C)OC2=O)C(Cl)=CC=1Cl)C>>[C:13]1([O:12][C:3]2[CH:2]=[CH:1][CH:6]=[CH:5][CH:4]=2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=C(O)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Agent: CC(C)Oc1cc(-n2nc(C(C)(C)C)oc2=O)c(Cl)cc1Cl
Agent: CCOc1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Agent: O=C([O-])c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Product: c1ccc(Oc2ccccc2)cc1

Procedure:
for instance, chloromethoxynil, biphenox, chloronitrophene (CNP), acifluorfen (i.e. 5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitrobenzoic acid and the like) and it's ethyl ester, acifluorfen-sodium, oxyfluorfen (i.e. 2-chloro-1-(3-ethoxy-4-nitrophenoxy)-4-trifluoromethylbenzene), or oxadiazol (for instance, oxadiazon (i.e. 3-[2,4-dichloro-5-(1-methylethoxy)phenyl]-5-(1,1-dimethylethyl)-1,3,4-oxadiazol-2(3H)-one) and the like);
Reaction SMILES: [OH:1][C:2]1[CH:17]=[CH:16][C:5]([C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])=[CH:4][CH:3]=1.[C:18](Cl)(=[O:30])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27](Cl)=[O:28]>>[CH2:9]([O:8][C:6]([C:5]1[CH:16]=[CH:17][C:2]([O:1][C:18](=[O:30])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([O:1][C:2]2[CH:3]=[CH:4][C:5]([C:6]([O:8][CH2:9][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)=[O:7])=[CH:16][CH:17]=2)=[O:28])=[CH:3][CH:4]=1)=[O:7])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=C(OCc1ccccc1)c1ccc(O)cc1
Reactant: O=C(Cl)CCCCCCCCC(=O)Cl
Product: O=C(CCCCCCCCC(=O)Oc1ccc(C(=O)OCc2ccccc2)cc1)Oc1ccc(C(=O)OCc2ccccc2)cc1

Procedure:
A similar procedure to Example 1 is carried out by using 16.7 g of benzyl p-hydroxybenzoate and 16.7 g of sebacic acid dichloride to yield di(p-benzyloxycarbonylphenyl)sebacate, m.p. 62.5°-63° C., as white crystals.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]2[CH2:10][C@H:9]2[C:11]([OH:13])=O)=[N:6][CH:7]=1.[C:14]([O:18][C:19](=[O:41])[NH:20][C@H:21]([CH2:26][NH:27][C:28]1[CH:37]=[CH:36][C:35]2[C:30](=[CH:31][CH:32]=[C:33]([CH:38]3[CH2:40][CH2:39]3)[CH:34]=2)[CH:29]=1)[C@@H:22]([CH3:25])[CH2:23][CH3:24])([CH3:17])([CH3:16])[CH3:15].C(N(CC)CC)C.FC1C=CC([C@@H]2C[C@H]2C(Cl)=O)=NC=1>O=S(Cl)Cl.C(Cl)Cl.O>[C:14]([O:18][C:19](=[O:41])[NH:20][C@H:21]([CH2:26][N:27]([C:28]1[CH:37]=[CH:36][C:35]2[C:30](=[CH:31][CH:32]=[C:33]([CH:38]3[CH2:39][CH2:40]3)[CH:34]=2)[CH:29]=1)[C:11]([C@@H:9]1[CH2:10][C@H:8]1[C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][N:6]=1)=[O:13])[C@@H:22]([CH3:25])[CH2:23][CH3:24])([CH3:16])([CH3:17])[CH3:15]
Reactant: O=C(O)[C@@H]1C[C@H]1c1ccc(F)cn1
Reactant: CC[C@H](C)[C@@H](CNc1ccc2cc(C3CC3)ccc2c1)NC(=O)OC(C)(C)C
Agent: O=C(Cl)[C@@H]1C[C@H]1c1ccc(F)cn1
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O
Product: CC[C@H](C)[C@@H](CN(C(=O)[C@@H]1C[C@H]1c1ccc(F)cn1)c1ccc2cc(C3CC3)ccc2c1)NC(=O)OC(C)(C)C
Temperature: 65 °C
Reaction time: 18 h

Procedure:
Trans-2-(5-fluoro-pyridin-2-yl)-cyclopropanecarboxylic acid (35 mg, 0.16 mmol) was dissolved in SOCl2 (2 mL) and was heated at 65° C. for 3 hrs. Removal of SOCl2 carefully under pump and dried the residue under high vacuum for 3 hrs. To a solution of {(1S,2S)-1-[(6-cyclopropyl-naphthalen-2-ylamino)-methyl]-2-methyl-butyl}-carbamic acid tert-butyl ester (55 mg, 0.14 mmol) and triethylamine (0.084 mL, 0.6 mmol) in DCM (3 mL) at 0° C. was added freshly made trans-2-(5-fluoro-pyridin-2-yl)-cyclopropanecarbonyl chloride in DCM (2 mL) slowly. The reaction mixture was then stirred at r.t. for 18 hrs. The reaction mixture was transferred to a separatory funnel containing water (20 mL). The aqueous layer was extracted with DCM (3×20 mL). The combined organic layers were washed with brine (20 mL), dried over MgSO4, filtered and concentrated. The residue was purified by Prep HPLC to afford [(1S,2S)-1-({(6-cyclopropyl-naphthalen-2-yl)-[trans-2-(5-fluoro-pyridin-2-yl)-cyclopropanecarbonyl]-amino}-methyl)-2-methyl-butyl]-carbamic acid tert-butyl ester as a solid: LC/MS (ESI) m/e 546 [(M+H)+, calcd for C33H40FN3O3 545.7].
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:7]=[C:6]([CH:8]([OH:11])[CH2:9]Br)[O:5][N:4]=1.[F:12][C:13]1[CH:26]=[CH:25][C:16]([C:17]([CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)=[O:18])=[CH:15][CH:14]=1.C(N(C(C)C)C(C)C)C>C(O)C>[F:12][C:13]1[CH:14]=[CH:15][C:16]([C:17]([CH:19]2[CH2:24][CH2:23][N:22]([CH2:9][CH:8]([C:6]3[O:5][N:4]=[C:3]([O:2][CH3:1])[CH:7]=3)[OH:11])[CH2:21][CH2:20]2)=[O:18])=[CH:25][CH:26]=1
Reactant: O=C(c1ccc(F)cc1)C1CCNCC1
Reactant: COc1cc(C(O)CBr)on1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCO
Product: COc1cc(C(O)CN2CCC(C(=O)c3ccc(F)cc3)CC2)on1

Procedure:
A solution of 3.5 g of 1-(3-methoxy-isoxazol-5-yl)-2-bromoethanol and 4.9 g of 4-(4'-fluorobenzoyl)piperidine and 5.4 ml of N-ethyldiisopropylamine in 160 ml of absolute ethanol was refluxed for 2 hours.
Reaction SMILES: [O:1]=[C:2]([CH2:8][CH2:9][NH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[P:17]([O-:24])([O:21][CH2:22][CH3:23])[O:18][CH2:19][CH3:20]>>[CH2:19]([O:18][P:17]([O:21][CH2:22][CH3:23])([C:2]([OH:1])([CH2:8][CH2:9][NH:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4])=[O:24])[CH3:20]
Reactant: CCOC(=O)C(=O)CCNc1ccccn1
Reactant: CCOP([O-])OCC
Product: CCOC(=O)C(O)(CCNc1ccccn1)P(=O)(OCC)OCC
Reaction time: 96 h

Procedure:
A mixture of 3.36 g (0.01 mole) of ethyl 2-oxo-4-(2-pyridylamino)butanoate in 6.9 g (0.05 mole) of diethyl phosphite is stirred at 20°-30° for 4 days. The excess diethyl phosphite is removed under vacuum on a rotary evaporator, and the crude product is purified by flash chromatography on silica gel using chloroform/ethanol as eluant.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([O:11][CH3:12])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O.[O:24]1[C:28]2([CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[O:27][CH2:26][CH2:25]1>O>[CH3:12][O:11][C:4]1[CH:3]=[C:2]([N:31]2[CH2:32][CH2:33][C:28]3([O:27][CH2:26][CH2:25][O:24]3)[CH2:29][CH2:30]2)[CH:7]=[CH:6][C:5]=1[N+:8]([O-:10])=[O:9]
Reactant: C1CC2(CCN1)OCCO2
Reactant: COc1cc(F)ccc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc(N2CCC3(CC2)OCCO3)ccc1[N+](=O)[O-]
Temperature: 70 °C
Reaction time: 8 h
Yield: 91.4 %

Procedure:
To a mixture of 4-fluoro-2-methoxy-1-nitrobenzene (5 g), potassium carbonate (10 g) and N,N-dimethylformamide (50 mL), 1,4-dioxa-8-azaspiro[4.5]decane (5 g) was added and stirred overnight at 70° C. The reaction mixture was diluted with water (150 mL), and the precipitated solid was collected by filtration and washed with diethyl ether to give 8-(3-methoxy-4-nitrophenyl)-1,4-dioxa-8-azaspiro[4.5]decane (7.86 g) as a light-yellow solid.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]([C:11]2[CH:15]=[C:14]([CH3:16])[N:13]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]([F:26])([F:25])[F:24])[C:12]=2[CH3:27])=[O:10])[CH:5]=[CH:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:35][C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=1>CN(C=O)C>[F:42][C:39]1[CH:40]=[CH:41][C:36]([CH2:35][O:1][C:2]2[CH:3]=[C:4]([NH:8][C:9]([C:11]3[CH:15]=[C:14]([CH3:16])[N:13]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=4[C:23]([F:26])([F:24])[F:25])[C:12]=3[CH3:27])=[O:10])[CH:5]=[CH:6][CH:7]=2)=[CH:37][CH:38]=1
Reactant: Fc1ccc(CBr)cc1
Reactant: Cc1cc(C(=O)Nc2cccc(O)c2)c(C)n1-c1ccccc1C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cc(C(=O)Nc2cccc(OCc3ccc(F)cc3)c2)c(C)n1-c1ccccc1C(F)(F)F
Temperature: 25 °C
Reaction time: 1 h
Yield: 29.6 %

Procedure:
Into an oven-dried 1 dram vial was added 2,5-dimethyl-1-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (3-hydroxy-phenyl)-amide (50 mg, 133 μmol), K2CO3 (22 mg, 160 μmol), 1-bromomethyl-4-fluoro-benzene (28 mg, 146 μmol) and 0.5 mL DMF. The vial was sealed and stirred 1 h at room temperature. The crude material was purified by reverse-phase chromatography (C18 column), eluting with 0.05% TFA in MeCN/H2O (30:70 to 90:10) to yield the title compound (19 mg, 30%) as an off-white solid. 1H-NMR (DMSO-d6): δ 9.43 (1H, s), 8.00 (1H, d, J=7.8), 7.90 (1H, t, J=7.8), 7.80 (1H, t, J=7.3), 7.58 (1H, m), 7.50 (3H, m), 7.35 (1H, d, J=8.6), 7.22 (3H, m), 6.69 (1H, d, J=8.3), 6.63 (1H, s), 5.07 (2H, s), 2.14 (3H, s), 1.88 (3H, s); MS (ESI): 483 (MH+).
Reaction SMILES: [CH3:1][C:2]([CH3:23])([CH:7]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[F:22])[C:8]1[C:9]([S:14][CH3:15])=[N:10][CH:11]=[N:12][CH:13]=1)[C:3]([O:5]C)=[O:4].C[S-].[Na+].Cl>CN(C)C=O>[CH3:1][C:2]([CH3:23])([CH:7]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[F:22])[C:8]1[C:9]([S:14][CH3:15])=[N:10][CH:11]=[N:12][CH:13]=1)[C:3]([OH:5])=[O:4]
Reactant: COC(=O)C(C)(C)C(c1ccccc1F)c1cncnc1SC
Agent: C[S-]
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Product: CSc1ncncc1C(c1ccccc1F)C(C)(C)C(=O)O
Reaction time: 0.5 h

Procedure:
A solution of 1.0 g (3.0 mmol) of methyl 2,2-dimethyl-3-(2-fluorophenyl)-3-(4-methylthio-5-pyrimidinyl)propanoate and 1.7 g (24 mmol) of sodium methanethiolate in 20 mL of dry N,N-dimethylformamide was heated to 50° C. with stirring for 30 minutes. The resulting solution was poured into dilute aqueous hydrochloric acid and the mixture obtained was extracted with ether. The ethereal extract was washed with water, dried over magnesium sulfate, filtered, and concentrated by evaporation under reduced pressure to obtain a light yellow solid. This solid was triturated in 30 mL of dichloromethane, collected by filtration, and dried under reduced pressure to obtain 570 mg (60 of theory) of the title compound as a light yellow solid melting at 204°-205° C.
Reaction SMILES: N[C:2]1[CH:11]=[C:10]([Cl:12])[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([Cl:13])[CH:3]=1.Cl.N([O-])=O.[Na+].[I-:19].[K+]>O.C(OCC)(=O)C>[Cl:12][C:10]1[CH:11]=[C:2]([I:19])[CH:3]=[C:4]([Cl:13])[C:5]=1[C:6]([O:8][CH3:9])=[O:7]
Reactant: COC(=O)c1c(Cl)cc(N)cc1Cl
Reactant: [I-]
Agent: Cl
Agent: O=N[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Product: COC(=O)c1c(Cl)cc(I)cc1Cl
Temperature: -5 °C
Reaction time: 0.5 h
Yield: 302.2 %

Procedure:
Methyl 4-amino-2,6-dichlorobenzoate (104 g, 0.14 mol) was added to concentrated hydrochloric acid (884 mL) and the mixture was cooled (−5° C.). A solution of sodium nitrite (55.2 g, 0.8 mol) in water (312 mL) was added dropwise with vigorous stirring, maintaining the reaction temperature in a range of −5° C. and 0° C. After 30 min, the mixture was filtered and the filtrate was added to a cooled (0° C.) and mechanically stirred solution of potassium iodide (352.3 g, 2.12 mol) in water (200 mL). The mixture was warmed to room temperature and stirred overnight. The reaction was diluted with ethyl acetate (1 L) and the organic phase was separated. The aqueous phase was extracted with ethyl acetate (1 L). The combined organic extracts were washed with saturated solution of NaHSO3, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc 50/1) to give methyl 2,6-dichloro-4-iodobenzoate (140 g, yield 90%) as a yellow oil. 1H NMR (CDCl3 400 MHz) δ 7.70 (s, 2H), 3.97 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][NH2:13])[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[Cl:20])[C:6]=2[CH:21]=1.O1CCCC1.[Cl:27][CH2:28][C:29](=O)[CH3:30].CO.C1C=CC=CC=1>CCOCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][N:13]=[C:29]([CH3:30])[CH2:28][Cl:27])[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[Cl:20])[C:6]=2[CH:21]=1
Reactant: CC(=O)CCl
Reactant: NNC1=Nc2ccc(Cl)cc2C(c2ccccc2Cl)=NC1
Solvent: CO
Solvent: CCOCC
Solvent: c1ccccc1
Product: CC(CCl)=NNC1=Nc2ccc(Cl)cc2C(c2ccccc2Cl)=NC1
Temperature: 25 °C

Procedure:
A mixture of 3.19 g. (0.01 mole) of 7-chloro-5-(o-chlorophenyl)-2-hydrazino-3H-1,4-benzodiazepine and 100 ml. of tetrahydrofuran, under nitrogen, was cooled to 0° C. and 1 ml. of chloropropanone was slowly added with stirring. The mixture was allowed to warm to room temperature; after one-half hour all the solid had dissolved. After stirring for a total of 2 hours, thin layer chromatography (SiO2, 20% methanol/benzene) showed essentially one spot. Evaporation at room temperature in vacuo gave a light brown gum which was dissolved in absolute ether and filtered. The solution was concentrated by a stream of N2 on a steam bath to a small volume and pentane was added. After cooling in the refrigerator, the resulting crystals were collected, washed with ether and pentane and dried, yielding 3.82 g. (97%) of 7-chloro-2-[(2-chloro-1-methylethylidene)hydrazinoe]-5-(o-chlorophenyl)-3H-1,4-benzodiazepine.
Reaction SMILES: C[O:2][C:3](=[O:31])[CH2:4][CH2:5][C@H:6]([C@@H:8]1[C@:25]2([CH3:26])[C@H:11]([C@H:12]3[C@H:22]([CH2:23][CH2:24]2)[C@:20]2([CH3:21])[C@@H:15]([CH2:16][C@H:17]([OH:27])[CH2:18][CH2:19]2)[C:14](=[CH:28][CH3:29])[C:13]3=[O:30])[CH2:10][CH2:9]1)[CH3:7]>O>[OH:27][C@@H:17]1[CH2:18][CH2:19][C@@:20]2([CH3:21])[C@H:15](/[C:14](=[CH:28]/[CH3:29])/[C:13](=[O:30])[C@@H:12]3[C@@H:22]2[CH2:23][CH2:24][C@@:25]2([CH3:26])[C@H:11]3[CH2:10][CH2:9][C@@H:8]2[C@H:6]([CH3:7])[CH2:5][CH2:4][C:3]([OH:31])=[O:2])[CH2:16]1
Reactant: CC=C1C(=O)[C@@H]2[C@H](CC[C@]3(C)[C@@H]([C@H](C)CCC(=O)OC)CC[C@@H]23)[C@@]2(C)CC[C@@H](O)C[C@@H]12
Solvent: O
Product: C/C=C1\C(=O)[C@@H]2[C@H](CC[C@]3(C)[C@@H]([C@H](C)CCC(=O)O)CC[C@@H]23)[C@@]2(C)CC[C@@H](O)C[C@@H]12

Procedure:
Compound 4 (258.37 g, 600 mmol, calculated as dried substance) was charged into an inert reactor. At a temperature of NMT 50° C., residual amounts of solvent were distilled off under vacuum. The residue was dissolved in methanol (360 mL) and water (54 mL) and caustic soda 50% wt. (54 mL) were added. The reaction mixture was heated up to 49° C. to 53° C. and stirred at this temperature for at least 2 hours. The pH of the reaction mixture is checked and verified to be >12. If the pH is <12, additional NaOH is added and the 2 hour reaction time is repeated. The solution was diluted with water (1000 mL) and the temperature was adjusted to 25° C. to 35° C. For the workup, reaction mixture was allowed to rest for at least 30 minutes. The phases were separated and the lower aqueous layer was transferred into a separate reactor and the organic layer was discarded. Ethyl acetate (1400 mL) and aqueous citric acid (244 g in 480 mL) were added with intensive stirring to the aqueous layer. The reaction mixture was stirred at 25° C. to 35° C. for 10 minutes. The phases were separated and the lower aqueous layer was discarded. Ethyl acetate was distilled off from the organic layer and replaced with ethyl acetate (800 mL). This operation was repeated until the water content of the distillate was NMT 1% or until a constant boiling point was reached. The suspension was cooled to 20° C. to 25° C., stirred for 30 minutes, and then the product was isolated and washed with ethyl acetate (100 mL, 3 to 4 times). Drying was done in a tumble dryer under vacuum at approximately 60° C. The yield is 118.71 g (47.5% from KLCA) of crude compound 5. Compound 4A, a mixture of E/Z isomers also can be used as starting material to produce compound 5A, a mixture of E/Z isomers.
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[C@@:29]2([CH3:30])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:28]2[CH2:27][CH2:26][C@@:25]2([CH3:31])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C:21]([OH:24])([CH3:23])[CH3:22])[CH2:12][C@@H:11]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:35])[CH3:34])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[K+].C1OCCOC2C(=CC=CC=2)OCCOCCOC2C(=CC=CC=2)OC1.[O:68]1[C:70]([CH3:72])([CH3:71])[CH2:69]1>C1(C)C=CC=CC=1.C(OCC)(=O)C.O>[Si:1]([O:8][C@@H:9]1[C@@:29]2([CH3:30])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:28]2[CH2:27][CH2:26][C@@:25]2([CH3:31])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C:21]([O:24][CH2:69][C:70]([OH:68])([CH3:72])[CH3:71])([CH3:23])[CH3:22])[CH2:12][C@@H:11]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:34])[CH3:35])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Si:1]([O:8][C@@H:9]1[C@@:29]2([CH3:30])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:28]2[CH2:27][CH2:26][C@@:25]2([CH3:31])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C:21]([OH:24])([CH3:23])[CH3:22])[CH2:12][C@@H:11]([O:32][Si:33]([C:36]([CH3:39])([CH3:38])[CH3:37])([CH3:34])[CH3:35])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CC1(C)CO1
Agent: CC(C)(O)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Agent: [H-]
Agent: [K+]
Solvent: O
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: CC(C)(O)COC(C)(C)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Temperature: 45 °C
Reaction time: 1.5 h
Yield: 19 %

Procedure:
A solution of 1α,3β-bis(tert-butyldimethylsilyloxy)-20-hydroxy-20-methylpregna-5,7,16-triene (49.2 mg, 0.0859 mmol), potassium hydride (35% in oil, 0.1 ml, 0.873 mmol) and dibenzo-18-crown-6 (30 mg, 0.0832 mmol) in toluene (0.2 ml) was stirred at room temperature for 3 min., 1,2-epoxy-2-methylpropane (60 mg, 0.832 mmol) was added and stirred at external temperature of 45° C. for 1.5 hours. The reaction solution was cooled with ice and water was added. The mixture was diluted with ethyl acetate, washed with saturated brine and the organic layer was dried over anhydrous magnesium sulfate. After evaporating under reduced pressure to remove the solvent, the thus obtained residue was purified by preparative thin layer chromatography (2 sheets (each 0.5 mm thickness), hexane:ethyl acetate=15:1, developed twice) to give the titled compound (10.4 mg, 19%) and 1α,3β-bis(tert-butyldimethylsilyloxy)-20-hydroxy-20-methylpregna-5,7,16-triene (18.6 mg, 38%), each as a colorless oil.
Reaction SMILES: [Cl-].[NH4+].C(O)(C)C.[CH3:7][O:8][C:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12]([N+:17]([O-])=O)=[CH:11][C:10]=1[S:20]([OH:23])(=[O:22])=[O:21]>O>[CH3:7][O:8][C:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12]([NH2:17])=[CH:11][C:10]=1[S:20]([OH:23])(=[O:22])=[O:21]
Reactant: COc1cc(OC)c(S(=O)(=O)O)cc1[N+](=O)[O-]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CC(C)O
Product: COc1cc(OC)c(S(=O)(=O)O)cc1N

Procedure:
A mixture solution prepared by adding 15 g of reduced iron, 0.3 g of ammonium chloride and 50 ml of isopropyl alcohol to 10 g of 2,4-dimethoxy-5-nitrobenzenesulfonic acid obtained in Step (2) above, was heated at 70° to 80° C. on a water bath with stirring, and 50 ml of water was added thereto. After stirring at 80° C. for 1 hour, the mixture was filtered while hot. To the filtrate, 20 ml of hydrochloric acid (d=1.18) was added. The crystals thus-precipitated were collected by filtration and washed with 20 ml of iropropyl alcohol.
Reaction SMILES: [CH:1]([C@@H:14]1[CH2:19][CH:18]=[CH:17][CH2:16][O:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C=C(Cl)C=C(C(OO)=[O:28])C=1.[O-]S([O-])=O.[Na+].[Na+]>C(Cl)Cl>[CH:1]([C@@H:14]1[CH2:19][C@@H:18]2[C@@H:17]([O:28]2)[CH2:16][O:15]1)([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C1=CC[C@@H](C(c2ccccc2)c2ccccc2)OC1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: c1ccc(C(c2ccccc2)[C@@H]2C[C@H]3O[C@H]3CO2)cc1
Reaction time: 20 h
Yield: 50.1 %

Procedure:
To a solution of (2S)-2-benzhydryl-3,6-dihydro-2H-pyran 27a (0.15 g, 0.6 mmol) in CH2Cl2 (20 ml) was added mCPBA (0.3 g, 70%, 1.2 mmol) in a portionwise manner at 0° C. The mixture was brought to room temperature and the reaction mixture was stirred for 20 h under N2. Na2SO3 (20 ml 1.0 M solution) was added to the reaction mixture at 0° C. to quench the reaction. The aqueous phase was extracted with CH2Cl2 (20 ml×2). The combined organic phase was washed in turn with saturated NaHCO3 and brine, then dried over anhydrous Na2SO4. Evaporation of the solvent gave light brown solid residue. The crude products were purified by flash chromatography on silica gel (hexane/ethyl ether=9:1) to give 0.08 g (1S,4S,6R)-4-benzhydryl-3,7-dioxa-bicyclo[4.1.0]-heptane 28a (50.3%, [α]D=(−) 60, c=1, MeOH) and 0.065 g 28b (1R,4S,6S)-4-benzhydryl-3,7-dioxa-bicyclo[4.1.0]-heptane (41%, [α]D=(−)76, c=1, MeOH).
Reaction SMILES: [S:1](Cl)([C:4]1[C:16]2[CH:15]=[CH:14][CH:13]=[C:9]([N:10]([CH3:12])[CH3:11])[C:8]=2[CH:7]=[CH:6][CH:5]=1)(=[O:3])=[O:2].ClCCl.C(N(CC)CC)C.[CH2:28]([NH2:31])[C:29]#[CH:30]>O1CCCC1>[S:1]([NH:31][CH2:28][C:29]#[CH:30])([C:4]1[C:16]2[CH:15]=[CH:14][CH:13]=[C:9]([N:10]([CH3:12])[CH3:11])[C:8]=2[CH:7]=[CH:6][CH:5]=1)(=[O:3])=[O:2]
Reactant: CN(C)c1cccc2c(S(=O)(=O)Cl)cccc12
Reactant: C#CCN
Solvent: ClCCl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: C#CCNS(=O)(=O)c1cccc2c(N(C)C)cccc12
Temperature: 25 °C
Reaction time: 12 h

Procedure:
234 mg of dansyl chloride (0.87 mmol) and 4.0 mL of anhydrous dichloromethane were placed in a 25 mL round-bottom flask equipped with a CaCl2 trap. 240 μL of triethylamine (1.73 mmol) and 330 μL of propargylamine (5.20 mmol) were added to the solution, which was then kept under stirring for 12 hours at room temperature. The residue obtained by distillation under reduced pressure was redissolved in some mL of tetrahydrofuran and the resulting mixture was filtrated. The evaporation of the solvent of the filtrated solution under reduced pressure affords the product in quantitative yield.
Reaction SMILES: [I:1][CH2:2][C:3]1[N:4]=[C:5]([C:14]2[CH:19]=[CH:18][C:17](C)=[CH:16][CH:15]=2)[O:6][C:7]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C1([C:27](=[O:32])C(=NO)C)CCCCC1.C(=O)C1C=CC=C(OC)C=1>>[I:1][CH2:2][C:3]1[N:4]=[C:5]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:32][CH3:27])[CH:15]=2)[O:6][C:7]=1[CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1
Reactant: CC(=NO)C(=O)C1CCCCC1
Reactant: Cc1ccc(-c2nc(CI)c(-c3ccccc3)o2)cc1
Agent: COc1cccc(C=O)c1
Product: COc1cccc(-c2nc(CI)c(C3CCCCC3)o2)c1

Procedure:
Analogously to the building block synthesis of 4-iodomethyl-5-phenyl-2-p-tolyloxazole, 1-cyclohexyl-1,2-propanedione-2-oxime and m-anis-aldehyde gave 4-iodomethyl-5-cyclohexyl-2-(3-methoxyphenyl)oxazole.
Reaction SMILES: N[C:2]1[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][NH:4][N:3]=1.[I:12]CI.N(OCCC(C)C)=O>>[I:12][C:2]1[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][NH:4][N:3]=1
Reactant: CCOC(=O)c1c[nH]nc1N
Reactant: ICI
Agent: CC(C)CCON=O
Product: CCOC(=O)c1c[nH]nc1I
Temperature: -10 °C
Reaction time: 2 h

Procedure:
A mixture of ethyl 3-amino-pyrazole-4-carboxylate (6.4 g, 40 mmole) and diiodomethane (200 g) was cooled to −10° C. Isoamyl nitrite (24 mL, 180 mmole) was added via a syringe over 30 minutes. The mixture was allowed to warm up to ambient temperature and then stirred at 100° C. for 2 hours. After cooling to room temperature, the mixture was concentrated and the residue was dissolved in ethyl acetate (200 mL) and washed with 0.5 M aqueous sodium metasulfite solution (2×70 mL), 1 N HCl and brine. The organic solution was dried with magnesium sulfate and concentrated. The crude product was purified on a silica gel column eluting with 15% ethyl acetate in hexane to provide the title compound. MS (DCI) m/e 266.9 (M+H)+, 283.9 (M+NH4)+.