Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3](=[O:31])[C@H:4]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=1)[NH:5][C:6](=[O:22])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[S:12]([C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=1)(=[O:14])=[O:13].[N:32]1([CH2:38][CH2:39]O)[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1>>[C:18]1([CH3:21])[CH:17]=[CH:16][C:15]([S:12]([N:8]2[CH2:9][CH2:10][CH2:11][C@H:7]2[C:6]([NH:5][C@H:4]([C:3]([OH:2])=[O:31])[CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH2:39][CH2:38][N:32]3[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]3)=[CH:26][CH:25]=2)=[O:22])(=[O:14])=[O:13])=[CH:20][CH:19]=1
Reactant: OCCN1CCCCC1
Reactant: COC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H]1CCCN1S(=O)(=O)c1ccc(C)cc1
Product: Cc1ccc(S(=O)(=O)N2CCC[C@H]2C(=O)N[C@@H](Cc2ccc(OCCN3CCCCC3)cc2)C(=O)O)cc1

Procedure:
The methyl ester was prepared by Mitsunobu reaction of N-(toluene-4-sulfonyl)-L-prolyl-L-tyrosine methyl ester with piperidineethanol following the procedure described for the preparation of Example 20 (284). The title compound was prepared using the procedure described in Method 7 as a solid, mp=102-106° C.
Reaction SMILES: [OH:1][CH:2]([CH:17]([OH:26])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH:11]([CH:13]([CH2:15][OH:16])[OH:14])[OH:12].C(O[C:31](=[O:33])[CH3:32])(=O)C>C(Cl)(Cl)Cl>[C:2]([C:15]([C:31](=[O:33])[CH3:32])([OH:16])[C:13]([C:13](=[O:14])[CH3:15])([OH:14])[C:11]([C:11](=[O:12])[CH3:10])([CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH:2]([OH:1])[CH:17]([OH:26])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[OH:12])(=[O:1])[CH3:3]
Reactant: CC(=O)OC(C)=O
Reactant: CCCCCCCCC(O)C(O)CCCCCCCCC(O)C(O)CO
Solvent: ClC(Cl)Cl
Product: CCCCCCCCC(O)C(O)CCCCCCCCC(O)(C(C)=O)C(O)(C(C)=O)C(O)(C(C)=O)C(C)=O
Reaction time: 2 h

Procedure:
0.2 g of the 9,10-dihydroxy-octadecyl glycerol (III) was dissolved in a small volume of chloroform (0.5 ml) in a screw tube and 2 ml acetic anhydride added. The reaction mixture was placed in a water bath for 2 h at 60° C., then dried down under a nitrogen stream. The residue was redissolved in chloroform:methanol:water (1:2:0.8) (v/v/v) and separated into phases by the addition of the appropriate amounts of chloroform and water to a final ratio of 1:1:0.9 (v/v/v). The synthesized compound (IV) is partioned in the chloroform phase.
Reaction SMILES: [NH2:1][CH:2]([C:6]([OH:8])=[O:7])[CH2:3][CH2:4][CH3:5].S(=O)(=O)(O)O.[CH2:14](O)[CH3:15]>>[CH2:14]([O:7][C:6](=[O:8])[CH:2]([NH2:1])[CH2:3][CH2:4][CH3:5])[CH3:15]
Reactant: CCCC(N)C(=O)O
Reactant: CCO
Agent: O=S(=O)(O)O
Product: CCCC(N)C(=O)OCC
Yield: 82 %

Procedure:
A suspension of 11.72 g of DL-norvaline in 90 ml of ethanol was combined with 3.6 ml of concentrated sulphuric acid and the mixture refluxed for eight days. A clear solution was formed, from which, after cooling, ethanol was removed by distillation. The residue was redissolved in 200 ml of distilled water and the pH adjusted to a value of between 10 and 12 by adding potassium carbonate. Extraction was then performed three times with 50 ml portions of ethyl acetate, the mixture washed once with 50 ml of a saturated sodium chloride solution and dried over sodium sulphate. Once the solvent had been removed by distillation, 11.93 g of 2-aminopentanoic acid ethyl ester (82% of th.) were obtained in the form of a yellowish oil.
Reaction SMILES: Cl.[CH3:2][O:3][C:4](=[O:11])[C@H:5]([C@H:7]([CH2:9][CH3:10])[CH3:8])[NH2:6].[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([S:19](Cl)(=[O:21])=[O:20])=[CH:15][CH:14]=1.C(N(CC)CC)C>C(Cl)Cl>[CH3:2][O:3][C:4](=[O:11])[C@H:5]([C@H:7]([CH2:9][CH3:10])[CH3:8])[NH:6][S:19]([C:16]1[CH:17]=[CH:18][C:13]([Cl:12])=[CH:14][CH:15]=1)(=[O:21])=[O:20]
Reactant: CC[C@H](C)[C@H](N)C(=O)OC
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC[C@H](C)[C@H](NS(=O)(=O)c1ccc(Cl)cc1)C(=O)OC
Temperature: 25 °C
Reaction time: 16 h
Yield: 110.4 %

Procedure:
To a solution of L-isoleucine methyl ester hydrochloride (1.82 g, 10 mmol) and 4-chlorobenzenesulfonyl chloride (2.11 g, 10 mmol) in CH2Cl2 was added triethylamine (4.18 mL, 30 mmol). The mixture was stirred at 25° C. for 16 hours, then filtered and concentrated. The crude product was purified by flash chromatography over silica gel using 10% ethyl acetate in hexane to give N-4-chlorobenzenesulfonyl L-isoleucine methyl ester 3.53 g.
Reaction SMILES: C([O:4][C:5]1[C:6]([CH3:33])=[C:7]2[C:12](=[C:13]([CH3:16])[C:14]=1[CH3:15])[O:11][CH:10]([CH2:17][O:18][C:19]1[CH:32]=[CH:31][C:22]([CH2:23][CH:24]3[S:28][C:27](=N)[NH:26][C:25]3=[O:30])=[CH:21][CH:20]=1)[CH2:9][CH2:8]2)(=O)C.Cl.[OH2:35]>COCCO>[OH:4][C:5]1[C:6]([CH3:33])=[C:7]2[C:12](=[C:13]([CH3:16])[C:14]=1[CH3:15])[O:11][CH:10]([CH2:17][O:18][C:19]1[CH:20]=[CH:21][C:22]([CH2:23][CH:24]3[S:28][C:27](=[O:35])[NH:26][C:25]3=[O:30])=[CH:31][CH:32]=1)[CH2:9][CH2:8]2
Reactant: O
Reactant: CC(=O)Oc1c(C)c(C)c2c(c1C)CCC(COc1ccc(CC3SC(=N)NC3=O)cc1)O2
Agent: Cl
Solvent: COCCO
Product: Cc1c(C)c2c(c(C)c1O)CCC(COc1ccc(CC3SC(=O)NC3=O)cc1)O2

Procedure:
290 mg of 5-[4-(6-acetoxy-5,7,8-trimethylchroman-2-ylmethoxy)benzyl]-2-iminothiazolidin-4-one (prepared as described in Example 4) were added to a mixture of 3 ml of concentrated hydrochloric acid, 1.5 ml of water and 5 ml of ethylene glycol monomethyl ether, and the mixture was heated under reflux for 3.5 hours. The reaction mixture was then processed and purified as described in Example 1(a), and the crude product, in the form of an oil, was subjected to column chromatography through silica gel. The title compound, melting at 158°-159° C., was obtained from the fractions eluted with a 4:1 by volume mixture of benzene and ethyl acetate.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)=[C:9]([C:13]2[N:17]([CH3:18])[N:16]=[N:15][N:14]=2)[C:10](O)=[O:11])=[CH:4][CH:3]=1.C(Cl)(=O)C([Cl:29])=O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)=[C:9]([C:13]2[N:17]([CH3:18])[N:16]=[N:15][N:14]=2)[C:10]([Cl:29])=[O:11])=[CH:4][CH:3]=1
Reactant: Cn1nnnc1C(C(=O)O)=C(c1ccc(F)cc1)c1ccc(F)cc1
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Product: Cn1nnnc1C(C(=O)Cl)=C(c1ccc(F)cc1)c1ccc(F)cc1

Procedure:
To a solution of dry (0.1 mmHg at 80° C.) 3,3-bis(4-fluorophenyl)-2-(1-methyl-1H-tetrazol-5-yl)-2-propenoic acid 3.8 g (11.0 mmoles) in 20 mL of dry methylene chloride was added 4 mL (46.0 mmoles) of purified oxalyl chloride (redistilled over CaH2) in one single portion. The reaction mixture was warmed gradually to reflux temperature for two hours. The mixture was evaporated under reduced pressure to remove volatile solvent, then excess oxalyl chloride was removed under vacuum (20 mmHg) at ambient temperature for 2 hours and under high vacuum (0.1 mmHg) at 50° C. for 16 hours to give the title compound.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1([C:13]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH2:8]1.C(Cl)(Cl)[Cl:28].ClN1C(=O)CCC1=O>O>[Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1([C:13]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[C:14]([Cl:28])[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:8]=[CH:9][CH:10]=[CH:11][CH2:12]1
Reactant: ClCCCCOC1(C(=Cc2ccccc2)c2ccccc2)C=CC=CC1
Reactant: ClC(Cl)Cl
Agent: O=C1CCC(=O)N1Cl
Solvent: O
Product: ClCCCCOC1(C(=C(Cl)c2ccccc2)c2ccccc2)C=CC=CC1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
Combine (E and Z)-1-(4-chlorobutoxy)phenyl-1,2-diphenyl ethylene (20.2 mol) and chloroform (60 L). Add N-chlorosuccinimide (7 kg, 52.4 mol). Heat to reflux. After 18 hours, cool to ambient temperature and add water. Separate the organic layer and extract with aqueous saturated sodium carbonate solution. Separate the organic layer and evaporate in vacuo to give (E and Z)-1-(4-chlorobutoxy)phenyl-2-chloro-1,2-diphenyl ethylene.
Reaction SMILES: [C:1]1([N:7]2[C:11]3[CH:12]=[C:13]([O:16][CH2:17][CH2:18][CH2:19][OH:20])[CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(C)=[O:29].OS(O)(=O)=O.O=[Cr](=O)=O>CC(C)=O>[C:1]1([N:7]2[C:11]3[CH:12]=[C:13]([O:16][CH2:17][CH2:18][C:19]([OH:29])=[O:20])[CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(C)=O
Reactant: OCCCOc1ccc2nc(-c3ccccc3)n(-c3ccccc3)c2c1
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Product: O=C(O)CCOc1ccc2nc(-c3ccccc3)n(-c3ccccc3)c2c1
Temperature: -15 °C
Reaction time: 3.5 h

Procedure:
100 mg of 3-[(1,2-diphenyl-1H-benzimidazol-6-yl)oxy]propan-1-ol was introduced into 2.5 ml of acetone and mixed at −15° C. with 0.15 ml of a solution of Jones reagent (produced from 0.27 g of chromium(VI) oxide, 1 ml of water and 0.23 ml of concentrated sulfuric acid). After 3.5 hours of stirring at −15° C., it was quenched with the addition of isopropanol. It was diluted with water, extracted three times with dichloromethane, the combined organic phases were dried on sodium sulfate and concentrated by evaporation in a vacuum. The residue was purified by chromatography on silica gel.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([N:11]2[C:15]3=[N:16][CH:17]=[CH:18][CH:19]=[C:14]3[C:13]([C:20]([NH:22][C:23]([NH2:25])=[NH:24])=[O:21])=[CH:12]2)=[CH:3][CH:2]=1.[Mg+2].[Cl-].[Cl-].C1N=C(N)C2N=CN([C@@H]3[O:42][C@H](COP(OP(OC[C@H]4O[C@@H](N5C=C(C(N)=O)CC=C5)[C@H](O)[C@@H]4O)(O)=O)(O)=O)[C@@H](O)[C@H]3OP(O)(O)=O)C=2N=1.C1C(=O)NC(=O)N([C@@H]2O[C@H](COP(OP(O[C@H]3O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]3O)(O)=O)(O)=O)[C@@H](O)[C@H]2O)C=1>C(#N)C>[OH:42][C:2]1[CH:3]=[C:4]([N:11]2[C:15]3=[N:16][CH:17]=[CH:18][CH:19]=[C:14]3[C:13]([C:20]([NH:22][C:23]([NH2:25])=[NH:24])=[O:21])=[CH:12]2)[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[N:1]=1
Reactant: NC(=O)C1=CN([C@@H]2O[C@H](COP(=O)(O)OP(=O)(O)OC[C@H]3O[C@@H](n4cnc5c(N)ncnc54)[C@H](OP(=O)(O)O)[C@@H]3O)[C@@H](O)[C@H]2O)C=CC1
Reactant: N=C(N)NC(=O)c1cn(-c2ccnc3ccccc23)c2ncccc12
Agent: O=C(O)[C@H]1O[C@H](OP(=O)(O)OP(=O)(O)OC[C@H]2O[C@@H](n3ccc(=O)[nH]c3=O)[C@H](O)[C@@H]2O)[C@H](O)[C@@H](O)[C@@H]1O
Agent: [Cl-]
Agent: [Mg+2]
Solvent: CC#N
Product: N=C(N)NC(=O)c1cn(-c2cc(O)nc3ccccc23)c2ncccc12
Reaction time: 2 h

Procedure:
4.8 mg of N-(1-quinolin-4-yl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-guanidine were dissolved using 150 ml of an aqueous solution containing 381 mg MgCl2, 1.3 mM NADPH (Dihydronicotinamide adenine dinucleotide phosphate, Calbiochem product number: 481973; Shen, A. L., et al. 1989. J. Biol. Chem. 264, 7584; Yamano, S., et al. 1989. Mol. Pharmacol. 36, 83.), 300 mg of human S9 fraction and 2.5 mM UDPGA (Uridine 5′-diphosphoglucuronic acid trisodium salt, Sigma catalog number U6751). The mixture was incubated for 120 minutes at 37° C. Then, 40 ml of acetonitrile were added, proteins centrifuged and decanted. This solution was concentrated to 100 ml and chromatographed using the system described below. The solvents were removed under reduced pressure to yield 0.9 mg of N-[1-(2-hydroxy-quinolin-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-guanidine as an amorphous solid.
Reaction SMILES: [CH3:1][N:2]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]([CH:11]1[CH2:18][CH2:17][CH2:16][CH2:15][NH:14][C:12]1=[O:13])=[O:10])[CH3:3].[C:19]1([CH3:30])[CH:24]=[CH:23][C:22]([S:25]([O:28]C)(=[O:27])=[O:26])=[CH:21][CH:20]=1.S([C:35]1C=CC(C)=CC=1)([O-])(=O)=O>C(#N)C>[C:19]1([CH3:30])[CH:20]=[CH:21][C:22]([S:25]([O-:28])(=[O:26])=[O:27])=[CH:23][CH:24]=1.[CH3:1][N+:2]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]([CH:11]1[CH2:18][CH2:17][CH2:16][CH2:15][NH:14][C:12]1=[O:13])=[O:10])([CH3:35])[CH3:3]
Reactant: CN(C)CCCCCC(=O)C1CCCCNC1=O
Reactant: COS(=O)(=O)c1ccc(C)cc1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Solvent: CC#N
Product: C[N+](C)(C)CCCCCC(=O)C1CCCCNC1=O
Temperature: 25 °C

Procedure:
In a 500 mL three-necked round-bottomed flask fitted with an argon inlet, condenser, and stir bar are placed amine amide 4 (17.94 g, 0.071 mol), acetonitrile (200 mL), and methyl p-toluenesulfonate (13.13 g, 0.071 mol). While adding the tosylate, the reaction mixture mildly exotherms. The mixture is heated to reflux for 3 h and is then cooled to room temperature. While concentrating the mixture by rotary evaporation, a tan solid forms which is redissolved in a minimal amount of acetonitrile and triturated with ether until a free flowing dispersion of the solid is obtained in the solvent system. The solid is collected by vacuum filtration under a blanket of nitrogen and transferred to a round-bottomed flask. The solid product is a suitable cationic bleach activator. It is dried at room temperature under vacuum (0.1 mmHg) for 24 h to give 5 (Cationic Bleach Activator A) (27.84 g, 90%) as an off-white solid, mp 128°-131° C. (softens at 118° C.).
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3](=[CH:8][CH2:9][CH3:10])[C:4]([F:7])([F:6])[F:5].[OH2:13]>>[F:1][C:2]([F:11])([F:12])[C:3]([OH:13])([CH2:8][CH2:9][CH3:10])[C:4]([F:6])([F:5])[F:7]
Reactant: O
Reactant: CCC=C(C(F)(F)F)C(F)(F)F
Product: CCCC(O)(C(F)(F)F)C(F)(F)F

Procedure:
As another example, 2-trifluoromethyl-1,1,1-trifluoro-2-pentanol may be prepared by fluorinating commercially available 2-pentenal to form 1,1,2,3-tetrafluoropentane which may then be dehydrogenated to form 1,1-difluoro-1-pentene. CF3 may then be reacted with the 1,1-difluoro-1-pentene to form 2-trifluoromethyl-1,1,1-trifluoropentane which may then be dehydrogenated to form 2-trifluoromethyl-1,1,1-trifluoro-2-pentene. The 2-trifluoromethyl-1,1,1-trifluoro-2-pentene may then be reacted with water to form 2-trifluoromethyl-1,1,1-trifluoro-2-pentanol.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([C:14]([OH:16])=O)[CH:11]=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH3:17][C:18]([CH3:26])([C:20]1[N:24]=[C:23]([CH3:25])[O:22][N:21]=1)[NH2:19]>>[CH3:17][C:18]([NH:19][C:14]([C:12]1[CH:11]=[CH:10][CH:9]=[C:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[N:13]=1)=[O:16])([C:20]1[N:24]=[C:23]([CH3:25])[O:22][N:21]=1)[CH3:26]
Reactant: Cc1nc(C(C)(C)N)no1
Reactant: O=C(O)c1cccc(-c2ccc(Cl)cc2)n1
Product: Cc1nc(C(C)(C)NC(=O)c2cccc(-c3ccc(Cl)cc3)n2)no1

Procedure:
The title compound was synthesized in analogy to Example 1, using 6-(4-chlorophenyl)-2-pyridinecarboxylic acid (CAN 135432-77-8) and α,α,5-trimethyl-1,2,4-oxadiazole-3-methanamine (CAN 1153831-97-0) as starting materials, MS (LC/MS): 357.1 (M+H).
Reaction SMILES: [NH2:1][C:2]1[C:7]([Br:8])=[C:6]([CH3:9])[C:5]([Br:10])=[CH:4][N:3]=1.OO.[OH2:13].[OH-:14].[Na+]>S(=O)(=O)(O)O>[N+:1]([C:2]1[C:7]([Br:8])=[C:6]([CH3:9])[C:5]([Br:10])=[CH:4][N:3]=1)([O-:14])=[O:13]
Reactant: O
Reactant: [OH-]
Reactant: Cc1c(Br)cnc(N)c1Br
Agent: O=S(=O)(O)O
Agent: OO
Agent: [Na+]
Product: Cc1c(Br)cnc([N+](=O)[O-])c1Br
Temperature: 10 °C
Yield: 33 %

Procedure:
2-amino-3,5-dibromo-4-methylpyridine (8 g, 30.0 mmol) was cooled to 10° C., followed by the addition of concentrated sulfuric acid(10 ml). The mixture was stirred, maintaining the temperature at 10° C. for 2 hrs, with the addition of a mixture of 30% hydrogen peroxide in 30% fuming sulfuric acid(25 ml/50 ml). The mixture was allowed to warm to room temperature and stirred for an additional 48 hrs. The reaction was then added to 300 ml of water with cooling and made very slightly basic with dropwise addition of 505 NaOH solution while the temperature was maintained at 20-25° C. The product was extracted using ether(4×150 ml) and dried with MgSO4. The solution was concentrated and purified by flash chromatography(2% MeOH/CH2Cl2) to give the desired product(2.94 g, 33%). 1H NMR (CDCl3): δ 8.45 (s, 1H), 2.68 (s, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:37]=[CH:36][C:6]([CH2:7][O:8][C:9]2[CH:10]=[C:11](C(OCC3C=CC=CC=3)(O)C)[CH:12]=[CH:13][C:14]=2[O:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=2)=[CH:5][CH:4]=1.[I-].[Na+].[CH3:40][C:41](C)=[O:42]>C(OCC)(=O)C>[CH3:24][O:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][O:15][C:14]2[C:9]([O:8][CH2:7][C:6]3[CH:36]=[CH:37][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)=[CH:10][CH:11]=[CH:12][C:13]=2[CH:41]([OH:42])[CH3:40])=[CH:18][CH:19]=1
Reactant: COc1ccc(COc2ccc(C(C)(O)OCc3ccccc3)cc2OCc2ccc(OC)cc2)cc1
Reactant: CC(C)=O
Agent: [I-]
Agent: [Na+]
Solvent: CCOC(C)=O
Product: COc1ccc(COc2cccc(C(C)O)c2OCc2ccc(OC)cc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 95 %

Procedure:
To a solution of 3,4-diacetoxy-ω-chloroacetophenone (2) (1.08 g: 4 mMol.) in acetone (11 ml) keeping at 0° C. is added sodium iodide (1.2 g: 2 Eq.), and the mixture is stirred at room temperature for 1 hour. The reaction mixture is diluted with ethyl acetate, washed with water, dried, and concentrated under reduced pressure to give 3,4-diacetoxy-ω-iodacetophenone (3) (1.38 g).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1)[C:5]([OH:7])=[O:6].[CH3:15]I.C[O-].[Na+]>CO>[CH3:15][O:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([C:11]([F:12])([F:13])[F:14])[CH:10]=1)[C:5]([OH:7])=[O:6]
Reactant: O=C(O)c1cc(O)cc(C(F)(F)F)c1
Reactant: CI
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: COc1cc(C(=O)O)cc(C(F)(F)F)c1

Procedure:
This product is prepared according to the procedure of Example 5 and comprises contacting 3-hydroxy-5-trifluoromethylbenzoic acid with methyl iodide in methanol containing sodium methoxide as the base, m.p. 131°-135° C.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH:7][C:8]1[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=1)[C:11]([OH:13])=[O:12]>C(O)C>[OH:7][C:8]1[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=1)[C:11]([O-:13])=[O:12].[NH2+:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: C1CCNCC1
Reactant: O=C(O)c1cccc(O)c1
Solvent: CCO
Product: C1CC[NH2+]CC1
Product: O=C([O-])c1cccc(O)c1

Procedure:
Piperidine (0.85 g; 10 mmol) was added dropwise to a solution of 3-hydroxybenzoic acid (1.38 g; 10 mmol) in ethanol (10 cm3). The solution was then left to stand at 5° C. in an open beaker for two weeks. This produced the desired product in the form of white crystals. The product was collected by filtration and recrystallized from water to produce translucent, colourless crystals. Found: C, 63.4%; H, 7.6%; N, 6.2%. Calculated for C12H17NO3 ; C, 64.55%; H, 7.69%; N, 6.24%. M.pt. 154°-156° C.
Reaction SMILES: [CH2:1]([O:3][C:4]([C@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[C:11](=[O:20])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([OH:19])[CH:14]=1)=[O:5])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:28][C:29]1[N:30]=[C:31]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:32][C:33]=1[CH3:34]>CN(C=O)C>[CH2:1]([O:3][C:4]([C@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[C:11](=[O:20])[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH2:28][C:29]2[N:30]=[C:31]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=3)[O:32][C:33]=2[CH3:34])[CH:14]=1)=[O:5])[CH3:2]
Reactant: Cc1oc(-c2ccccc2)nc1CCl
Reactant: CCOC(=O)[C@H]1CCCN1C(=O)Cc1cccc(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)[C@H]1CCCN1C(=O)Cc1cccc(OCc2nc(-c3ccccc3)oc2C)c1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a solution of the title A compound, (R)-1-[2-(3-hydroxy-phenyl)-acetyl]-pyrrolidine-2-carboxylic acid ethyl ester (1.0 g, 3.61 mmol) in 10 mL DMF is added potassium carbonate (0.60 g, 4.33 mmol) followed by 4-chloromethyl-5-methyl-2-phenyl-oxazole (0.75 g, 3.61 mmol). The mixture is stirred for 24 h at RT, and partitioned between ethyl acetate and water. The organic layer is separated and washed with brine, dried over anhydrous sodium sulfate, concentrated and purified by flash chromatography (silica gel) eluting with hexane:ethyl acetate (3:7) to give (R)-1-{2-[3-(5-methyl-2-phenyl-oxazol-4-ylmethoxy)-phenyl]-acetyl}-pyrrolidine-2-carboxylic acid ethyl ester.
Reaction SMILES: [C:1]([CH2:4][N:5]([C:10]1[CH:15]=[C:14]([O:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[CH:27]=[C:26]([O:31]CC2C=CC=CC=2)[C:25]([O:39]CC2C=CC=CC=2)=[CH:24]3)[CH:13]=[C:12]([O:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH3:65])[CH:11]=1)[CH2:6][C:7]([OH:9])=[O:8])([OH:3])=[O:2]>[Pd].C1COCC1>[C:7]([CH2:6][N:5]([C:10]1[CH:11]=[C:12]([O:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH3:65])[CH:13]=[C:14]([O:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[CH:27]=[C:26]([OH:31])[C:25]([OH:39])=[CH:24]3)[CH:15]=1)[CH2:4][C:1]([OH:3])=[O:2])([OH:9])=[O:8]
Reactant: CCCCCCCCCCCCCCCCCCOc1cc(OCCCCc2ccc3cc(OCc4ccccc4)c(OCc4ccccc4)cc3c2)cc(N(CC(=O)O)CC(=O)O)c1
Agent: [Pd]
Solvent: C1CCOC1
Product: CCCCCCCCCCCCCCCCCCOc1cc(OCCCCc2ccc3cc(O)c(O)cc3c2)cc(N(CC(=O)O)CC(=O)O)c1
Reaction time: 6 h
Yield: 90.3 %

Procedure:
A mixture of 1.16 g of N-(carboxymethyl)-N-[3-(octadecyloxy)-5-[4-[2,3-bis(phenylmethoxy)-6-naphthalenyl]butoxy]phenyl]glycine and 0.35 g of 10% palladium on carbon in 75 ml of THF was stirred under a hydrogen atmosphere until uptake ceased after 6 hours. The catalyst was removed by filtration through a Celite padand the filtrate was concentrated to a solid which was triturated with hexane and filtered to give 0.835 g (90% yield, mp 153°-155°) of N-(carboxymethyl)-N-[3-[4-(2,3-dihydroxy-6-naphthalenyl)butoxy]-5-(octadecyloxy)phenyl]glycine.
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([C:7](Cl)=[O:8])=[CH:4][CH:3]=1.[N:10]1([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][NH2:20])[CH:14]=[CH:13][N:12]=[CH:11]1.[OH-].[Na+]>C(Cl)Cl>[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][N:10]2[CH:14]=[CH:13][N:12]=[CH:11]2)=[O:8])=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1ccc(Cl)s1
Reactant: NCCCCCn1ccnc1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: O=C(NCCCCCn1ccnc1)c1ccc(Cl)s1
Reaction time: 20 h

Procedure:
A solution of 1.8 g. of 5-chlorothiophene-2-carbonyl chloride in 10 ml. of CH2Cl2 was added to a mixture of 1.52 g. of 1H-imidazole-1-pentanamine, 10 ml. of 1N NaOH and 50 ml. of CH2Cl2. The reaction mixture was stirred for 20 hours and then treated with 25 ml. of CH2Cl2 and 5 ml. of 1N NaOH. The layers were separated and the organic layer was washed with water, dried over MgSO4 and concentrated. The crystalline residue was washed with diethyl ether whereby the desired product, m.p. 123°-125° C., was obtained.
Reaction SMILES: S(Cl)([Cl:3])=O.[C:5]1([CH2:11][CH2:12][C:13]([OH:15])=O)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1>C(Cl)Cl>[C:5]1([CH2:11][CH2:12][C:13]([Cl:3])=[O:15])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)CCc1ccccc1
Solvent: ClCCl
Product: O=C(Cl)CCc1ccccc1
Reaction time: 8 h

Procedure:
Thionyl chloride (21.8 mL, 300 mmol) was added to a solution of 3-phenylpropionic acid (15 g, 99.9 mol) in DCM (40 mL) and was stirred overnight. The mixture was concentrated in vacuo to yield intermediate (7a), which was used in the next step without further purification.