Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:8])([F:7])[S:3]([OH:6])(=[O:5])=[O:4].N#N.[CH:11]1([NH:17][C:18](=[O:51])[C@H:19]([CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)[NH:20]C([C@@]2(NC(=O)C3C=CC=CC=3)CCC3C(=C(OC)C=CC=3)C2)=O)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1>CO>[F:1][C:2]([F:8])([F:7])[S:3]([OH:6])(=[O:5])=[O:4].[CH:11]1([NH:17][C:18](=[O:51])[C@H:19]([CH2:44][C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)[NH2:20])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1
Reactant: COc1cccc2c1C[C@@](NC(=O)c1ccccc1)(C(=O)N[C@@H](Cc1ccccc1)C(=O)NC1CCCCC1)CC2
Agent: N#N
Agent: O=S(=O)(O)C(F)(F)F
Solvent: CO
Product: N[C@@H](Cc1ccccc1)C(=O)NC1CCCCC1
Reaction time: 4 h
Yield: 83.5 %

Procedure:
7.1 ml (80.74 mmol) of trifluoromethanesulphonic acid were added dropwise under argon and while cooling with ice to a suspension of 7.5 g (13.54 mmol) of N2 -[(R)-2-benzamido-8-methoxy-1,2,3,4-tetrahydro-naphthalene-2-carbonyl]-L-phenylalanine cyclohexylamide in 35 ml of methanol. The mixture was stirred at 80° in a bomb tube for 4 hours, then cooled and subsequently concentrated to a volume of ~20 ml. 50 ml of dichloromethane were added while stirring, the suspension was filtered and the fitter residue was washed with dichloromethane and dried, 4.48 g (83%) of L-phenylalanine cyclohexylamide trifluoromethanesulphonate being isolated. The filtrate was washed with water, dried over MgSO4 and concentrated. The residue was chromatographed on 350 g of silica gel with ethyl acetate/hexane (2:3), whereupon 4.0 g (87%) of methyl (S)-2-benzamido-8-methoxy-1,2,3,4-tetrahydro-naphthalene-2-carboxylate were obtained. [α]D =+144.0° (CHCl3, c=0.2). IR(KBr): 3366w(br.), 3062w, 2998w, 2948w, 1739s, 1647s, 1586m, 1527s, 1468s, 1437m, 1292m, 1259s, 1099m, 1047m, 774w, 713m. (D. Obrecht, Helv. Chim. Acta 1992, 75, 1666).
Reaction SMILES: [CH:1]1[C:12]2[C:11]3([CH2:14][CH2:13]3)[C:10]3[CH:15]=[CH:16][CH:17]=[CH:18][C:9]=3[O:8][CH:7]([C:19]([OH:21])=[O:20])[O:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.S(=O)(=O)(O)O.[CH3:27]O>>[CH:15]1[C:10]2[C:11]3([CH2:13][CH2:14]3)[C:12]3[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=3[O:6][CH:7]([C:19]([O:21][CH3:27])=[O:20])[O:8][C:9]=2[CH:18]=[CH:17][CH:16]=1
Reactant: CO
Reactant: O=C(O)C1Oc2ccccc2C2(CC2)c2ccccc2O1
Agent: O=S(=O)(O)O
Product: COC(=O)C1Oc2ccccc2C2(CC2)c2ccccc2O1
Reaction time: 3 h

Procedure:
The crude spiro(cyclopropane-1,12'(12'H)-dibenzo[d,g][1,3]dioxocin)-6'-carboxylic acid from Example 3 was dissolved in 500 ml of methanol and 2.0 ml of sulfuric acid added. The mixture was heated at reflux and stirred for 3 hours. About half of the methanol was removed by evaporation under reduced pressure and the remaining solution was diluted with 1.5 l of ether. The solution obtained was extracted several times with water and then with brine and was then dried over magnesium sulfate, filtered, and concentrated by evaporation under reduced pressure to obtain the title compound in impure form. This was purified by filtration chromatography, eluting with a 9:1 mixture of hexane and ether to obtain the product as a pale yellow crystalline solid. This was recrystallized from methanol to obtain 9.55 g of the title compound as pale tan crystals melting at 123°-126° C. The proton and carbon NMR and infrared spectra were consistent with the assigned structure.
Reaction SMILES: [CH2:1]([NH:6][C:7]1[N:12]=[CH:11][CH:10]=[CH:9][N:8]=1)[CH2:2][CH2:3][C:4]#[CH:5].[C:13](OC(=O)C)(=[O:15])[CH3:14]>S(=O)(=O)(O)O>[C:13]([N:6]([C:7]1[N:8]=[CH:9][CH:10]=[CH:11][N:12]=1)[CH2:1][CH2:2][CH2:3][C:4]#[CH:5])(=[O:15])[CH3:14]
Reactant: C#CCCCNc1ncccn1
Reactant: CC(=O)OC(C)=O
Agent: O=S(=O)(O)O
Product: C#CCCCN(C(C)=O)c1ncccn1
Temperature: 90 °C

Procedure:
A mixture of 2-(pent-4-ynylamino)pyrimidine (4.25 g, 26.4 mmol) and concentrated sulfuric acid (5 drops) in acetic anhydride (100 mL) was heated to 90° C. for 16 h. The mixture was cooled and partitioned between water and methylene chloride. The organic layer was dried (Na2SO4), filtered through a pad of silica and evaporated in vacuo to give the title compound:
Reaction SMILES: [OH-].[Na+].[CH2:3]([O:5][C:6]1[CH:33]=[CH:32][C:9]2[N:10]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([NH2:29])=[CH:25][C:24]=3[O:30][CH3:31])(=[O:22])=[O:21])[C:11](=[O:19])[N:12]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[C:8]=2[CH:7]=1)[CH3:4].Cl[C:35]([O:37][C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)=[O:36]>O.C1COCC1>[CH2:3]([O:5][C:6]1[CH:33]=[CH:32][C:9]2[N:10]([S:20]([C:23]3[CH:28]=[CH:27][C:26]([NH:29][C:35]([O:37][C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)=[O:36])=[CH:25][C:24]=3[O:30][CH3:31])(=[O:21])=[O:22])[C:11](=[O:19])[N:12]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[C:8]=2[CH:7]=1)[CH3:4]
Reactant: O=C(Cl)Oc1ccccc1
Reactant: CCOc1ccc2c(c1)n(C1CCCCC1)c(=O)n2S(=O)(=O)c1ccc(N)cc1OC
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CCOc1ccc2c(c1)n(C1CCCCC1)c(=O)n2S(=O)(=O)c1ccc(NC(=O)Oc2ccccc2)cc1OC
Reaction time: 5 h

Procedure:
0.29 g of NaOH pellets in 2 ml of water was added at 5° C., with stirring, to a solution of 1.1 g of 5-ethoxy-1,3-dihydro-1-(2-methoxy-4-aminobenzenesulfonyl)-3-cyclo-hexyl-2H-benzimidazol-2-one, obtained in Example 5 step B), in 25 ml of THF. 1 ml of phenyl chloroformate was then added with continued stirring. The reaction mixture was then stirred for 5 hours, the temperature being allowed to rise to 20° C. The mixture was then concentrated under vacuum, the residue was taken up with water, extracted with ether and washed with water and the organic phase was dried over sodium sulfate and concentrated under vacuum. 1 g of the expected product was obtained by crystallization from iso ether. M.p.=197° C.
Reaction SMILES: [O:1]=[S:2]1(=[O:10])[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8]O.O=S(Cl)[Cl:13].C([O-])(O)=O.[Na+]>C(Cl)Cl>[Cl:13][CH2:8][CH2:7][N:3]1[CH2:4][CH2:5][CH2:6][S:2]1(=[O:10])=[O:1]
Reactant: O=S(Cl)Cl
Reactant: O=S1(=O)CCCN1CCO
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: O=S1(=O)CCCN1CCCl
Temperature: 40 °C
Yield: 29.6 %

Procedure:
To a solution of 2-(1,1-dioxo-1λ6-isothiazolidin-2-yl)-ethanol (0.14 g, 0.847 mmol) in DCM (4 mL) was added SOCl2 (0.151 g, 1.27 mmol) and the reaction mixture was heated to 40° C. for 2 h. The mixture was cooled to room temperature, diluted with DCM, poured into a sat. NaHCO3 solution (10 mL) and the aqueous layer was extracted with DCM (2×20 mL). Combined organics were dried over Na2SO4, filtered and evaporated to dryness to give the title compound (0.046 g, 30%) as an orange oil which was used with no further purification. MS: 184.1 (M+H+).
Reaction SMILES: I[C:2]1[N:3]=[C:4]([CH3:7])[S:5][CH:6]=1.[CH2:8]([C:12]1[S:13][C:14]2[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=2[N:16]=1)[CH2:9][C:10]#[CH:11]>>[CH3:7][C:4]1[S:5][CH:6]=[C:2]([C:11]#[C:10][CH2:9][CH2:8][C:12]2[S:13][C:14]3[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=3[N:16]=2)[N:3]=1
Reactant: C#CCCc1nc2ccccc2s1
Reactant: Cc1nc(I)cs1
Product: Cc1nc(C#CCCc2nc3ccccc3s2)cs1
Yield: 52.8 %

Procedure:
The title compound was prepared in accordance with the general method of Example 1, from 4-iodo-2-methyl-thiazole (120 mg, 0.53 mmol) and 2-but-3-ynyl-benzo[d]thiazole (100 mg, 0.53 mmol, Example 35(A)). The crude residue was purified by flash chromatography (cyclohexane/AcOEt 4:1) to yield 152 mg (0.28 mmol, 53%) of 2-(4-(2-methylthiazol-4-yl)but-3-ynyl)benzo[d]thiazole as a yellow solid.
Reaction SMILES: [CH3:1][N:2](C)[CH2:3][CH2:4][CH2:5][CH:6]1[C:10]2([CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[O:9][C:8]2[CH:17]=[CH:18][CH:19]=[CH:20][C:7]1=2.C(=O)(O)[O-].[Na+].Cl[C:28]([O:30][CH2:31][CH3:32])=[O:29].O>C1(C)C=CC=CC=1>[CH2:31]([O:30][C:28](=[O:29])[N:2]([CH2:3][CH2:4][CH2:5][CH:6]1[C:10]2([CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]2)[O:9][C:8]2[CH:17]=[CH:18][CH:19]=[CH:20][C:7]1=2)[CH3:1])[CH3:32]
Reactant: CN(C)CCCC1c2ccccc2OC12CCCCCC2
Reactant: CCOC(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Product: CCOC(=O)N(C)CCCC1c2ccccc2OC12CCCCCC2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred mixture, kept under nitrogen, of 7.85 g of 3-(3-dimethylaminopropyl)-spiro[benzofuran-2(3H),1'-cycloheptane] and 11.7 g of powdered sodium bicarbonate in 250 ml of toluene was added 5.2 ml of ethyl chloroformate. The mixture was refluxed overnight and thereafter an additional 2.6 ml of ethyl chloroformate was added. The mixture was refluxed for another 5 hours and thereafter stirred overnight at room temperature. Water (250 ml) was then added with stirring. The organic phase was separated and washed successively with 2N-hydrochloric acid, water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo to an oil. This material was used as such for subsequent synthesis. The IR, NMR and Mass Spectra were in accord with the designated structure.
Reaction SMILES: [C:1]1([C:7]#[C:8][C:9]([O:11][C:12]2[CH:17]=[C:16]([CH3:18])[C:15]([Br:19])=[C:14]([CH3:20])[CH:13]=2)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>ClCCl.FC(F)(F)C(O)=O.ClCCCl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Br:19][C:15]1[C:16]([CH3:18])=[C:17]2[C:12](=[CH:13][C:14]=1[CH3:20])[O:11][C:9](=[O:10])[CH:8]=[C:7]2[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Cc1cc(OC(=O)C#Cc2ccccc2)cc(C)c1Br
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: ClCCCl
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1cc2oc(=O)cc(-c3ccccc3)c2c(C)c1Br
Reaction time: 2 h
Yield: 76.8 %

Procedure:
To a stirring solution of 4-bromo-3,5-dimethyl-phenyl 3-phenylpropiolate (1-1) (9839 mg, 30.00 mmol) in dichloromethane (15 mL) and trifluoroacetic acid (45 mL) was added palladium acetate (350 mg, 1.60 mmol) under ice-cooling. After stirred for 2 h under ice-cooling, the mixture was diluted with 1,2-dichloroethane and evaporated to dryness. The residue was chromatographed on a silica gel (chloroform:hexanes=1:1-3:2) to give the title compound 1-2 (7581 mg, 77% yield) as a dark yellow solid.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:25][S:26](O)(=[O:28])=[O:27]>C(Cl)(Cl)Cl>[CH2:7]([C:1]1[CH:6]=[CH:5][C:4]([S:26]([Cl:25])(=[O:28])=[O:27])=[CH:3][CH:2]=1)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]
Reactant: O=S(=O)(O)Cl
Reactant: CCCCCCCCCCCCCCCCCCc1ccccc1
Solvent: ClC(Cl)Cl
Product: CCCCCCCCCCCCCCCCCCc1ccc(S(=O)(=O)Cl)cc1
Temperature: 25 °C
Reaction time: 22 h
Yield: 56 %

Procedure:
To a solution of 1-phenyloctadecane (0.84 g, 2.5 mmol) in CHCl3 (5 mL) was added chlorosulfonic acid (0.5 mL, 7.5 mmol) and the mixture was stirred at rt for 22 h. The mixture was poured on ice and extracted with CH2Cl2. The combined extracts were washed with water, a solution of NaHCO3, and water, dried (Na2SO4), and concentrated in vacuo. The residue was chromatographed on silica gel (70-230 mesh) with hexane/ethyl acetate (49:1) to give the product as a white solid (0.60 g, 1.4 mmol, 56%), mp 43-44° C.; 1H NMR (300 MHz, CDCl3) δ 0.86 (t, 3H, J=6.9 Hz), 1.25 (m, 30H), 1.65 (m, 2H), 2.72 (t, 2H, J=7.8 Hz), 7.42 (d, 2H, J=8.4 Hz), 7.93 (d, 2H, J=8.4 Hz); 13C NMR (75 MHz, CDCl3) 14.1, 22.7, 29.2, 29.4, 29.5, 29.7, 30.9, 31.9, 36.0, 127.1, 129.6, 141.8, 151.7.
Reaction SMILES: [N:1]1([CH2:6][C@@H:7]2[CH2:11][C@@H:10](OS(C)(=O)=O)[CH2:9][N:8]2[C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=2)=[O:18])[CH:5]=[CH:4][N:3]=[CH:2]1.[C:30]([SH:33])(=[O:32])[CH3:31].[H-].[Na+]>CN(C)C=O>[C:30]([S:33][C@@H:10]1[CH2:9][N:8]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=2)=[O:18])[C@H:7]([CH2:6][N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)[CH2:11]1)(=[O:32])[CH3:31]
Reactant: CS(=O)(=O)O[C@@H]1C[C@@H](Cn2ccnc2)N(C(=O)OCc2ccc([N+](=O)[O-])cc2)C1
Reactant: CC(=O)S
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(=O)S[C@H]1C[C@@H](Cn2ccnc2)N(C(=O)OCc2ccc([N+](=O)[O-])cc2)C1
Temperature: 0 °C

Procedure:
A solution of (2S,4R)-2-(imidazol-1-yl)methyl-4-methanesulfonyloxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (0.76 g) in dimethylformamide (2 ml) was added to a mixture of thioacetic S-acid (0.16 ml) and sodium hydride (62.8 % in oil suspension, 0.08 g) in dimethylformamide (5 ml) under nitrogen stream and the mixture was heated at 70°-75° C. for 5 hours. The mixture was poured into ice-water (70 ml), extracted with ethyl acetate (70 ml), dried over magnesium sulfate and concentrated under reduced pressure to give a syrup. The syrup was subjected to a column chromatography on silica gel (20 g) and eluted with a mixture of methanol and chloroform (2:98, V/V) to give (2S,4S)-4-acetylthio-2-(imidazol-1-yl)methyl-1-(-4-nitrobenzyloxycarbonyl)pyrrolidine (0.38 g).
Reaction SMILES: O=[C:2]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].Cl.[NH2:18][OH:19].C([O-])(=O)C.[Na+]>C(O)C>[OH:19]/[N:18]=[C:2](/[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)\[CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7]
Reactant: NO
Reactant: CCOC(=O)CCCC(=O)c1ccccc1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)CCC/C(=N\O)c1ccccc1
Yield: 88.4 %

Procedure:
A mixture of ethyl 5-oxo-5-phenylpentanoate (8.00 g), hydroxylamine hydrochloride (3.03 g), sodium acetate (4.47 g) and ethanol (70 ml) was heated under reflux for 15 hours. The reaction mixture was concentrated, and the residue was diluted with water and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4), and then concentrated. The residue was subjected to column chromatography on silica gel, and ethyl E-5-hydroxyimino-5-phenylpentanoate (7.55 g, yield 88%) was obtained as crystals from a fraction eluted with ethyl acetate-hexane (1:3, v/v). Recrystallization from hexane gave colorless crystals. m.p. 28-30° C.
Reaction SMILES: C(N(CC)CC)C.[CH:8](=O)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.Cl.[NH2:17][CH:18]([C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([Cl:31])[CH:25]=1)[C:19]([O:21][CH2:22][CH3:23])=[O:20]>C(#N)C>[CH2:22]([O:21][C:19](=[O:20])[CH:18]([N:17]=[CH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([Cl:31])[CH:25]=1)[CH3:23]
Reactant: O=Cc1ccccc1
Reactant: CCOC(=O)C(N)c1ccc(Cl)c(Cl)c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CCOC(=O)C(N=Cc1ccccc1)c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Triethylamine (170 mL) and benzaldehyde (130 mL) were added to a suspension of ethyl amino-(3,4-dichlorophenyl)-acetate hydrochloride (350 g) in acetonitrile (1.5 L), followed by stirring at room temperature overnight. The insoluble matter was removed through Celite, followed by washing with ethyl acetate. The filtrate was subjected to partitioning with water and then extraction with ethyl acetate. The thus-obtained organic layer was washed with saturated brine, and then dried over sodium sulfate anhydrate. The solvent was removed under reduced pressure, to thereby give the title compound (425 g). The title compound was used in the next step without further purification.
Reaction SMILES: [C:1]([O:5][C:6](=[O:23])[NH:7][CH:8]([C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=1)[C:9](=[O:14])N(OC)C)([CH3:4])([CH3:3])[CH3:2].Br[C:25]1[C:26]([CH3:38])=[CH:27][C:28]([O:31][CH:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)=[N:29][CH:30]=1>>[C:1]([O:5][C:6](=[O:23])[NH:7][CH:8]([C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[C:17]([Cl:22])[CH:16]=1)[C:9]([C:25]1[CH:30]=[N:29][C:28]([O:31][CH:32]2[CH2:33][CH2:34][O:35][CH2:36][CH2:37]2)=[CH:27][C:26]=1[CH3:38])=[O:14])([CH3:2])([CH3:3])[CH3:4]
Reactant: Cc1cc(OC2CCOCC2)ncc1Br
Reactant: CON(C)C(=O)C(NC(=O)OC(C)(C)C)c1ccc(Cl)c(Cl)c1
Product: Cc1cc(OC2CCOCC2)ncc1C(=O)C(NC(=O)OC(C)(C)C)c1ccc(Cl)c(Cl)c1

Procedure:
The title compound was prepared from rac-[(3,4-dichloro-phenyl)-(methoxy-methyl-carbamoyl)-methyl]-carbamic acid tert-butyl ester (Intermediate 9) and 5-bromo-4-methyl-2-(tetrahydro-pyran-4-yloxy)-pyridine (Intermediate 19) in analogy to Example 1a): MS (ISN): 493.1 and 495.3 (M−H)−.
Reaction SMILES: BrCCCCCC(C)C(OCC)=O.CC(CCCCI)CC(OC)=O.O1CCCCC1[O:32][CH:33]([CH2:53][CH2:54][CH2:55][CH2:56][CH3:57])[CH2:34][CH2:35][CH2:36][N:37]([CH2:42][CH2:43][CH2:44][CH2:45][CH:46](C)[CH2:47][C:48]([O:50]C)=[O:49])[S:38]([CH3:41])(=[O:40])=[O:39]>>[OH:32][C@H:33]([CH2:53][CH2:54][CH2:55][CH2:56][CH3:57])[C:34]#[C:35][CH2:36][N:37]([CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][C:48]([OH:50])=[O:49])[S:38]([CH3:41])(=[O:39])=[O:40]
Reactant: CCCCCC(CCCN(CCCCC(C)CC(=O)OC)S(C)(=O)=O)OC1CCCCO1
Agent: CCOC(=O)C(C)CCCCCBr
Agent: COC(=O)CC(C)CCCCI
Product: CCCCC[C@@H](O)C#CCN(CCCCCCC(=O)O)S(C)(=O)=O

Procedure:
The synthesis of this compound is carried out as described in Example 8 except that, in Step A, the ethyl 7-bromo-2-methylheptanoate is replaced by an equimolar amount of methyl 3-methyl-7-iodoheptanoate. The product of Step A is thus methyl 7-{N-[4-(2-tetrahydropyranyloxy)nonyl]methanesulfonamido}-3-methylheptanoate. The subsequent hydrolysis step yields 7-[N-(4-hydroxynonyl)methanesulfonamido]-3-methylheptanoic acid (B).
Reaction SMILES: O[C:2]1([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([O:30][CH3:31])[CH:25]=2)[C:6]2[C:7]([CH3:21])=[C:8]([NH:13][C:14](=[O:20])[CH2:15][C:16]([CH3:19])([CH3:18])[CH3:17])[C:9]([CH3:12])=[C:10]([CH3:11])[C:5]=2[O:4][C:3]1([CH3:23])[CH3:22]>C(OCC)(=O)C.CCCCCC>[CH3:31][O:30][C:26]1[CH:25]=[C:24]([CH:2]2[C:6]3[C:7]([CH3:21])=[C:8]([NH:13][C:14](=[O:20])[CH2:15][C:16]([CH3:17])([CH3:18])[CH3:19])[C:9]([CH3:12])=[C:10]([CH3:11])[C:5]=3[O:4][C:3]2([CH3:23])[CH3:22])[CH:29]=[CH:28][CH:27]=1
Reactant: COc1cccc(C2(O)c3c(C)c(NC(=O)CC(C)(C)C)c(C)c(C)c3OC2(C)C)c1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: COc1cccc(C2c3c(C)c(NC(=O)CC(C)(C)C)c(C)c(C)c3OC2(C)C)c1
Yield: 77 %

Procedure:
Using N-(3-hydroxy-3-(3-methoxyphenyl)-2,2,4,6,7-pentamethyl-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamide obtained in Example 259, the title compound was synthesized in the same manner as in Example 271. Yield: 77%. Melting point: 166-167° C. (ethyl acetate-hexane).
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:7][CH2:8][CH3:9])[CH:5]=[CH2:6])[CH3:2].[CH2:10]([O:12][SiH:13]([O:17][CH2:18][CH3:19])[O:14][CH2:15][CH3:16])[CH3:11]>>[CH2:1]([O:3][CH:4]([O:7][CH2:8][CH3:9])[CH2:5][CH2:6][Si:13]([O:17][CH2:18][CH3:19])([O:14][CH2:15][CH3:16])[O:12][CH2:10][CH3:11])[CH3:2]
Reactant: C=CC(OCC)OCC
Reactant: CCO[SiH](OCC)OCC
Product: CCOC(CC[Si](OCC)(OCC)OCC)OCC

Procedure:
A round-bottomed flask is introduced with 2 g (1.1 equivalent) of 3,3-diethoxy-1-propene produced in Example 1, and 2 ml (1 equivalent) of triethoxysilane commercially available from Aldrich, Co. Then, hydrogen hexachloroplatinate (H2PtCl6), a metal catalyst, is added in the amount of 1 ppm to the solution. After that, the resulting mixture is allowed to react at 100° C. under atmospheric pressure for 48 hours. Next, the resulting material is fractionally distilled under a vacuum, thereby giving 4.2 g of colorless 3,3-diethoxyprophyltriethoxysilane. The product is dissolved in CDCl3 and measured for 1NMR and infrared-absorbing spectrum. Results are shown in FIGS. 1 and 2.
Reaction SMILES: [Br:1][CH:2]([CH2:11]Br)[C:3]([CH3:10])([CH3:9])[C:4]([O:6][CH2:7]C)=[O:5].[OH-].[K+]>CO.O>[Br:1][C:2](=[CH2:11])[C:3]([CH3:10])([CH3:9])[C:4]([O:6][CH3:7])=[O:5]
Reactant: CCOC(=O)C(C)(C)C(Br)CBr
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: C=C(Br)C(C)(C)C(=O)OC
Yield: 39.4 %

Procedure:
Ethyl 3,4-dibromo-2,2-dimethylbutanoate (6.3 g), prepared as described in Example 3 above, was treated with 3.6 g of potassium hydroxide in 50 mL of 4:1 methanol:water and stirred 16 hours at ambient temperature. The solution was diluted with 100 mL of water and extracted with ether. The organic layer was washed with a saturated brine solution, dried and concentrated in vacuo to give 1.7 g of methyl 3-bromo-2,2-dimethylbut-3-enoate as an oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N:9]2[C:13](=[O:14])[NH:12][N:11]=[N:10]2)=[CH:4][C:3]=1[CH:15]=[CH:16][C:17]([O:19][CH2:20][CH3:21])=[O:18].[F:22][CH2:23][CH2:24][CH2:25]CS([O-])(=O)=O.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N:9]2[C:13](=[O:14])[N:12]([CH2:25][CH2:24][CH2:23][F:22])[N:11]=[N:10]2)=[CH:4][C:3]=1[CH:15]=[CH:16][C:17]([O:19][CH2:20][CH3:21])=[O:18]
Reactant: O=S(=O)([O-])CCCCF
Reactant: CCOC(=O)C=Cc1cc(-n2nn[nH]c2=O)c(F)cc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)C=Cc1cc(-n2nnn(CCCF)c2=O)c(F)cc1Cl
Temperature: 0 °C
Reaction time: 18 h
Yield: 24.6 %

Procedure:
To a stirred mixture of 2.62 g (0.00830 mole) of ethyl 3-[2-chloro-4-fluoro-5-(1,4-dihydro-5-oxo-5H-tetrazol-1-yl)phenyl]propenoate in 20 mL of N,N-dimethylformamide was added 1.46 g (0.00939 mole) of 3-fluoropropylmethane sulfonate and 1.30 g (0.00939 mole) of potassium carbonate. The reaction mixture was heated at 50°-60° C. and was stirred at that temperature for approximately 18 hours. The mixture was cooled and was poured into ice water. This mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and was filtered. The filtrate was evaporated under reduced pressure to yield 0.76 g of ethyl 3-[2-chloro-4-fluoro-5-[4-(3-fluoropropyl)-1,4-dihydro-5-oxo-5H-tetrazol -1yl]phenyl]propenoate as an oil, compound 4 of Table 1.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([O:11][CH3:12])[CH:5]=1)([O-:3])=[O:2].Br[N:14]1[C:18](=O)[CH2:17][CH2:16][C:15]1=O.N1CCCC1>N(C(C)(C)C#N)=NC(C)(C)C#N.C(Cl)(Cl)(Cl)Cl>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)=[C:6]([O:11][CH3:12])[CH:5]=1)([O-:3])=[O:2]
Reactant: O=C1CCC(=O)N1Br
Reactant: COc1cc([N+](=O)[O-])ccc1C
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: C1CCNC1
Solvent: ClC(Cl)(Cl)Cl
Product: COc1cc([N+](=O)[O-])ccc1CN1CCCC1
Temperature: 0 °C
Reaction time: 1 h
Yield: 80 %

Procedure:
A mixture of 4-nitro-2-methoxytoluene (5 g, 30 mmol), N-bromosuccinimide (5.3 g, 30 mmol), azobisisobutyronitrile (AIBN, 10 mg) and CCl4 was refluxed for 60 h. The reaction mixture was cooled to 0° C., filtered through diatomaceous earth and concentrated under vacuum. The resulting oil was redissolved in THF (50 mL) and added portionwise to a cold (0° C.) stirred solution of pyrrolidine (10.65 g, 150 mmol). Afterwards, the cooling bath was removed and the reaction was stirred at ambient temperature for 1 h. It was then concentrated to an oil, diluted with 100 mL saturated aqueous NaHCO3 and 50 mL brine. Following extraction three times with 125 mL EtOAc, the combined organic layer was dried over MgSO4 and concentrated to 6.5 g of an oil. Purification by chromatography (SiO2 ; 30% EtOAc in hexanes) yielded 5.7 g (24 mmol, 80%) of the desired compound as an oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:8]12[C:14](=[O:15])[O:13][C:11](=[O:12])[CH:9]1[CH2:10]2.[Cl-].[Al+3].[Cl-].[Cl-].CN(C)C=O>Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:14]([C@H:8]2[CH2:10][C@H:9]2[C:11]([OH:13])=[O:12])=[O:15])=[CH:4][CH:3]=1
Reactant: O=C1OC(=O)C2CC12
Reactant: Clc1ccccc1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: CN(C)C=O
Product: O=C(c1ccc(Cl)cc1)[C@H]1C[C@H]1C(=O)O
Temperature: 0 °C
Reaction time: 1 h

Procedure:
4.5 g (0.040 mol) of chlorobenzene and 5.0 g (0.0446 mol) of 1,2-cyclopropanedicarboxylic acid anhydride were successively added dropwise to a mixture of 60.0 g (0.45 mol) of anhydrous aluminium chloride and 9 mL (0.115 mol) of anhydrous dimethylformamide while maintaining a reaction temperature of 60° C. to 70° C. and the mixture was then kept at 70° C. for 1 hour. After cooling, the reaction mixture was stirred into a mixture of 500 g of crushed ice and 60 mL of concentrated hydrochloric acid, the precipitate was suction filtered, washed thoroughly with water and dried over Siccapent in a vacuum drying chamber at a temperature of 50° C. 7.8 g (87% of theoretical) of colorless crystals were obtained, m.p. 150° C.-153° C.