Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([CH:8]1[CH2:15][CH2:14][CH2:13][CH:12]([OH:16])[CH2:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)=O.OS(O)(=O)=O.O=[Cr](=O)=O.S(=O)(=O)(O)O.[Cr](O)(O)(=O)=O>CC(C)=O.CC(O)C.O>[CH2:1]([CH:8]1[CH2:9][CH2:10][CH2:11][C:12](=[O:16])[CH2:13][CH2:14][CH2:15]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OC1CCCC(Cc2ccccc2)CCC1
Agent: O=[Cr](=O)(O)O
Agent: O=[Cr](=O)=O
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CC(C)O
Solvent: CC(C)=O
Product: O=C1CCCC(Cc2ccccc2)CCC1
Temperature: 25 °C
Yield: 95.5 %

Procedure:
1.3 g of 5-benzyl-1-cyclooctanol prepared in the aforementioned Reference Example 1 was dissolved in 40 ml of acetone. To the solution was added 2.5 ml Jones reagent which was prepared in the ratio of 11.5 ml of sulfuric acid, 13 g of chromic acid and 20 ml of water. The reaction solution was stirred at room temperature for twenty minutes. To the reaction solution was added 2 ml of 2-propanol, followed by filtration through Celite. The residue was washed with dichloromethane and the washing liquid was combined with the filtrate. The filtrate was washed with water and a saturated saline solution, and dried over anhydrous sodium sulfate. The solvent was evaporated. The crude product was subject to column chromatography on silica gel, and the eluate with ethyl acetate-hexane (1:15) was collected, to afford 1.23 g of the titled compound as colorless liquid.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH:11]([CH3:14])[CH2:10][CH2:9]2)[C:5]([N+:15]([O-:17])=[O:16])=[CH:4][N:3]=1.[CH3:18][N:19]1[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1>CN(C=O)C>[CH3:18][N:19]1[CH2:24][CH2:23][N:22]([C:2]2[N:7]=[C:6]([N:8]3[CH2:13][CH2:12][CH:11]([CH3:14])[CH2:10][CH2:9]3)[C:5]([N+:15]([O-:17])=[O:16])=[CH:4][N:3]=2)[CH2:21][CH2:20]1
Reactant: CN1CCNCC1
Reactant: CC1CCN(c2nc(Cl)ncc2[N+](=O)[O-])CC1
Solvent: CN(C)C=O
Product: CC1CCN(c2nc(N3CCN(C)CC3)ncc2[N+](=O)[O-])CC1
Temperature: 80 °C
Yield: 63 %

Procedure:
To a solution of 2-chloro-4-(4-methyl-piperidin-1-yl)-5-nitro-pyrimidine (as prepared in the previous step) (257 mg, 1.00 mmol) in DMF (10 mL) was added 1-methyl piperazine (110 μL, 1.00 mmol). The resulting mixture was heated at 80° C. for 48 h. The reaction mixture was allowed to cool to room temperature and partitioned between water/EtOAc. The EtOAc layer was separated, dried (Na2SO4) and concentrated in vacuo. The residue obtained was purified on silica (0-10% MeOH:EtOAc) to obtain the title compound (192 mg, 63%). 1H-NMR (CDCl3; 400 MHz): δ 8.76 (s, 1H), 3.90 (br m, 6H), 2.96 (m, 2H), 2.40 (m, 4H), 2.32 (s, 3H), 1.82-1.6 (m, 3H), 1.2-1.3 (m, 2H), 1.02 (d, 3H, J=6.5 Hz).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][N:5]([C:8]2[S:9][C:10]([C:14]([OH:16])=O)=[C:11]([CH3:13])[N:12]=2)[C:4](=[O:17])[CH:3]=1.[F:18][C:19]1[CH:20]=[C:21]([CH2:25][NH2:26])[CH:22]=[CH:23][CH:24]=1>>[F:18][C:19]1[CH:20]=[C:21]([CH:22]=[CH:23][CH:24]=1)[CH2:25][NH:26][C:14]([C:10]1[S:9][C:8]([N:5]2[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][C:4]2=[O:17])=[N:12][C:11]=1[CH3:13])=[O:16]
Reactant: NCc1cccc(F)c1
Reactant: Cc1nc(-n2ccc(O)cc2=O)sc1C(=O)O
Product: Cc1nc(-n2ccc(O)cc2=O)sc1C(=O)NCc1cccc(F)c1
Yield: 44 %

Procedure:
Following the procedure as described in Example 1, making variations only as required to use 2-(4-hydroxy-2-oxopyridin-1(2H)-yl)-4-methylthiazole-5-carboxylic acid in place of 4-methyl-2-(2-oxo-4-phenylpyridin-1(2H)-yl)thiazole-5-carboxylic acid to react with (3-fluorophenyl)methanamine, the title compound was obtained as a colorless solid in 44% yield: mp 250-252° C. (ethyl acetate/hexanes); 1H NMR (300 MHz, DMSO-d6) δ 11.50 (br s, 1H), 8.78 (t, J=6.0 Hz, 1H), 8.59 (d, J=8.0 Hz, 1H), 7.39-7.30 (m, 1H), 7.13-7.00 (m, 3H), 6.26 (dd, J=8.0, 2.5 Hz, 1H), 5.82 (d, J=2.5 Hz, 1H), 4.39 (d, J=5.9 Hz, 2H), 2.53 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 167.9, 164.2, 162.1, 161.6, 154.2, 142.9, 142.8, 132.6, 130.7, 123.7, 123.4, 114.5, 114.1, 104.4, 98.0, 42.6, 17.5; MS (ES+) m/z: 360.2 (M+1).
Reaction SMILES: [O:1](S(C(F)(F)F)(=O)=O)[S:2]([C:5]([F:8])([F:7])[F:6])(=[O:4])=[O:3].[CH2:16]([N:23]([CH3:35])[C@H:24]1[CH2:33][CH2:32][C:31]2[C:30](O)=[CH:29][CH:28]=[CH:27][C:26]=2[CH2:25]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.CCN(CC)CC.[O-]S(C(F)(F)F)(=O)=O>C(Cl)Cl.CO.C(Cl)Cl>[F:6][C:5]([F:8])([F:7])[S:2]([O:1][C:30]1[C:31]2[CH2:32][CH2:33][C@H:24]([N:23]([CH2:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH3:35])[CH2:25][C:26]=2[CH:27]=[CH:28][CH:29]=1)(=[O:4])=[O:3]
Reactant: CN(Cc1ccccc1)[C@H]1CCc2c(O)cccc2C1
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: CCN(CC)CC
Solvent: CO
Solvent: ClCCl
Product: CN(Cc1ccccc1)[C@H]1CCc2c(cccc2OS(=O)(=O)C(F)(F)F)C1
Reaction time: 0.25 h
Yield: 24 %

Procedure:
Tf2O (3.6 mL, 21.309 mmol) was dropwise added to a −78° C. cooled solution of (6S)-6-[benzyl(methyl)amino]-5,6,7,8-tetrahydronaphthalen-1-ol (5.30 g, 19.822 mmol) and Et3N (6 mL, 43.04 mmol) in CH2Cl2 (100 mL). Addition time: ca. 5 min. The reaction was completed after 15 min at low temperature (TLC analysis). The reaction mixture was poured into CH2Cl2 (250 mL) and washed with H2O (200 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The crude residue was flash chromatographed on silica gel (1-2-3% MeOH/CH2Cl2), to furnish two batches of product: 5.78 g of pure triflate, and 1.90 g of product slightly impure (TLC analysis) (Rf=0.8 (10% MeOH/CH2Cl2), off-white solid, 73% and 24% yield).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C@H:11]([C:19]([OH:21])=O)[CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[CH3:22][C:23]1(C)OC(=O)CC(=O)[O:24]1.S([O-])(O)(=O)=O.[K+]>CN(C1C=CN=CC=1)C.O1CCCC1>[CH2:12]([CH:11]1[C:19]([OH:21])=[CH:22][C:23](=[O:24])[N:10]1[C:4]1[CH:5]=[CH:6][C:7]([C:8]#[N:9])=[C:2]([Cl:1])[CH:3]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: N#Cc1ccc(N[C@@H](Cc2ccccc2)C(=O)O)cc1Cl
Reactant: CC1(C)OC(=O)CC(=O)O1
Agent: CN(C)c1ccncc1
Agent: O=S(=O)([O-])O
Agent: [K+]
Solvent: C1CCOC1
Product: N#Cc1ccc(N2C(=O)C=C(O)C2Cc2ccccc2)cc1Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 65.3 %

Procedure:
To a solution of N-(3-chloro-4-cyanophenyl)phenylalanine (2.0 g), Meldrum's acid (1.05 g) and 4-(N,N-dimethylamino)pyridine (1.22 g) in tetrahydrofuran (30 mL) was added N,N′-carbonyldiimidazole (1.29 g) at 0° C., and the mixture was stirred at room temperature overnight. A 5% aqueous potassium hydrogen sulfate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with 5% aqueous potassium hydrogen sulfate solution and saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (30 mL), and the mixture was refluxed for 45 min. After allowing to room temperature, the mixture was extracted 3 times with saturated aqueous sodium hydrogen carbonate solution. The aqueous layers were combined, and acidified with citric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was recrystallized from tetrahydrofuran-hexane to give the title compound as pale-yellow crystals (yield: 1.41 g, 65%).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:19]=[C:18]([CH2:20][OH:21])[O:17][N:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(=O)(=O)=O.C(N(CC)CC)C.[NH4+].[Cl-]>CS(C)=O.C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:19]=[C:18]([CH:20]=[O:21])[O:17][N:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCc1cc(-c2ccc(OCc3ccccc3)cc2)no1
Agent: O=S(=O)=O
Agent: [Cl-]
Agent: [NH4+]
Solvent: CS(C)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=Cc1cc(-c2ccc(OCc3ccccc3)cc2)no1

Procedure:
[3-(4-benzyloxy-phenyl)-isoxazol-5-yl]-methanol (1.0 g, 3.5 mmol) was dissolved in 60 ml of DMSO/methylene chloride (1:2), to which solution were added dropwise sulfur trioxide.pyridine complex (1.6 g, 10.5 mmol) and triethylamine (2.44 ml, 17.5 mmol), and stirred at 0° C. for about 2 hours. The completion of the reaction was confirmed by TLC, and 10 ml of NH4Cl was added to the solution. The residual solvent was distilled under reduced pressure, and then extracted three times with water and methylene chloride. An organic layer was washed with saline solution. The obtained organic layer was distilled under reduced pressure, followed by column chromatography (ethyl acetate/Hexane=1:2) to obtain 3-(4-benzyloxy-phenyl)-isoxazol-5-carbaldehyde as a desired solid compound.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:51]=[CH:50][CH:49]=[CH:48][C:10]=1[CH2:11][C:12]1[C:13]([O:24][C@@H:25]2[O:42][C@H:41]([CH2:43][O:44]C(=O)C)[C@@H:36]([O:37]C(=O)C)[C@H:31]([O:32]C(=O)C)[C@H:26]2[O:27]C(=O)C)=[N:14][NH:15][C:16]=1[C:17]([F:23])([F:22])[C:18]([F:21])([F:20])[F:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[O-].[Na+]>O1CCCC1.CO>[CH2:1]([O:8][C:9]1[CH:51]=[CH:50][CH:49]=[CH:48][C:10]=1[CH2:11][C:12]1[C:13]([O:24][C@@H:25]2[O:42][C@H:41]([CH2:43][OH:44])[C@@H:36]([OH:37])[C@H:31]([OH:32])[C@H:26]2[OH:27])=[N:14][NH:15][C:16]=1[C:17]([F:23])([F:22])[C:18]([F:19])([F:21])[F:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(=O)OC[C@H]1O[C@@H](Oc2n[nH]c(C(F)(F)C(F)(F)F)c2Cc2ccccc2OCc2ccccc2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: OC[C@H]1O[C@@H](Oc2n[nH]c(C(F)(F)C(F)(F)F)c2Cc2ccccc2OCc2ccccc2)[C@H](O)[C@@H](O)[C@@H]1O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 4-(2-benzyloxybenzyl)-5-pentafluoroethyl-1,2-dihydropyrazol-3-one (55 mg) and acetobromo-α-D-glucose (63 mg) in acetonitrile (2 mL) was added potassium carbonate (23 mg), and the mixture was stirred at room temperature for 3 days. The reaction mixture was purified by column chromatography on aminopropyl silica gel (eluent: ethyl acetate/hexane=1/1-ethyl acetate) to give 4-(2-benzyloxybenzyl)-5-pentafluoroethyl-3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-1H-pyrazole. To a solution of 4-(2-benzyloxybenzyl)-5-pentafluoroethyl-3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-1H-pyrazole in tetrahydrofuran (1 mL) and methanol (0.5 mL) was added sodium methoxide (28% methanol solution, 50 μL), and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=10/1-5/1) to give the title compound (33 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[CH3:8].O[C@H:11]([CH3:16])[C:12]([O:14][CH3:15])=[O:13]>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[CH3:8])[O:9][C@@H:11]([CH3:16])[C:12]([O:14][CH3:15])=[O:13]
Reactant: Cc1ccc(O)cc1Cl
Reactant: COC(=O)[C@@H](C)O
Product: COC(=O)[C@H](C)Oc1ccc(C)c(Cl)c1

Procedure:
The title compound was prepared following the same protocol as described in Step 1, Example 42, using the 3-chloro-4-methylphenol instead of the m-cresol and the (R)-methyl 2-hydroxypropanoate instead of the (S)-methyl 2-hydroxypropanoate.
Reaction SMILES: [NH2:1][CH:2]([C:6]1[O:7][CH2:8][CH2:9][S:10][CH:11]=1)[C:3]([OH:5])=[O:4].[C:12]([O:16][C:17](N=[N+]=[N-])=[O:18])([CH3:15])([CH3:14])[CH3:13].C(N(CC)CC)C>CN(C)C=O>[C:12]([O:16][C:17]([NH:1][CH:2]([C:6]1[O:7][CH2:8][CH2:9][S:10][CH:11]=1)[C:3]([OH:5])=[O:4])=[O:18])([CH3:15])([CH3:14])[CH3:13]
Reactant: CC(C)(C)OC(=O)N=[N+]=[N-]
Reactant: NC(C(=O)O)C1=CSCCO1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NC(C(=O)O)C1=CSCCO1
Temperature: 35 °C
Reaction time: 48 h
Yield: 65.6 %

Procedure:
DL-α-Amino-(5,6-dihydro-1,4-oxathiin-2-yl)-acetic acid (25.4 g.) is suspended in dimethylformamide (435 cc.); tert.-butoxycarbonyl azide (41.5 g.) and triethylamine (51 cc.) are added. The reagents are left in contact for 48 hours whilst stirring at a temperature of 35° C. The solution is concentrated under reduced pressure (1 mm Hg), the residue is taken up in water (300 cc.), and the pH is adjusted to 8.5 by adding a saturated sodium bicarbonate solution. The aqueous phase is extracted twice with ethyl ether (a total of 500 cc.) which is discarded, and is then acidified to pH = 3 by adding 4 N hydrochloric acid A product precipitates, which is filtered off and then dissolved in methylene chloride (600 cc.). The solution obtained is dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (20 mm Hg). DL-α-Tert.-butoxycarbonylamino-(5,6-dihydro-1,4-oxathiin-2-yl)-acetic acid (26.2 g.), melting at 160° C is thus obtained.
Reaction SMILES: [F:1][C:2]1([F:12])[O:6][C:5]2[CH:7]=[CH:8][C:9]([CH3:11])=[CH:10][C:4]=2[O:3]1.[Br:13]N1C(=O)CCC1=O>C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C(Cl)(Cl)(Cl)Cl>[F:12][C:2]1([F:1])[O:6][C:5]2[CH:7]=[CH:8][C:9]([CH2:11][Br:13])=[CH:10][C:4]=2[O:3]1
Reactant: Cc1ccc2c(c1)OC(F)(F)O2
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: FC1(F)Oc2ccc(CBr)cc2O1
Yield: 96.6 %

Procedure:
A mixture of 2,2-difluoro-5-methyl-1,3-benzodioxole (29.0 g, 0.169 mole), N-bromosuccinimide (30.1 g, 0.169 mole), benzoyl peroxide (0.5 g) and carbon tetrachloride (50 ml) is refluxed for 2.5 hours. Carbon tetrachloride (50 ml) is then added to the hot reaction mixture and the solids are filtered off. The filtrate and washings are evaporated to yield 41.0 g of title product, a brown oil; nmr (CCl4) δ 4.38 (S, 2H), 6.8-7.4 (m, 3H). The product is used without further purification in the next step.
Reaction SMILES: [Mg].Br[C:3]1C=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:9]([C:17]1[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=1)(=O)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[Cl-].[NH4+].[O:25]1CCC[CH2:26]1>>[C:10]1([C:9]2[C:19]([C:18]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[N:20][CH:21]=[CH:22][C:17]=2[CH2:26][OH:25])[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: C1CCOC1
Reactant: O=C(c1ccccc1)c1ccncc1
Reactant: Brc1ccccc1
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Product: OCc1ccnc(-c2ccccc2)c1-c1ccccc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 97 %

Procedure:
A Grignard reagent was prepared from magnesium (0.21 g, 8.64 mmol) (Wako Pure Chemical Industries, Ltd.) and bromobenzene (1.35 g, 8.60 mmol) (Wako Pure Chemical Industries, Ltd.). 4-Benzoylpyridine (0.52 g, 28.4 mmol) (Wako Pure Chemical Industries, Ltd.) was dissolved in tetrahydrofuran (10 mL) (Wako Pure Chemical Industries, Ltd.), and the Grignard reagent was added dropwise, followed by stirring at room temperature for 5 hours. A saturated aqueous solution of ammonium chloride (Wako Pure Chemical Industries, Ltd.) was added to the reaction solution, and mixture was extracted with ethyl acetate (Wako Pure Chemical Industries, Ltd.). The organic layer was dried with anhydrous sodium sulfate (Wako Pure Chemical Industries, Ltd.), and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography (chloroform (Wako Pure Chemical Industries, Ltd.) as an eluent), to thereby obtain the title compound (0.72 g, 97% yield).
Reaction SMILES: [CH3:1][O:2][CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([O:15][CH3:16])=[C:9]([C:11](=O)[CH2:12][CH3:13])[CH:10]=1.C(OP([CH2:25]/[CH:26]=[CH:27]/[C:28]([O:30][CH2:31][CH3:32])=[O:29])(OCC)=O)C>>[CH3:1][O:2][CH2:3][O:4][C:5]1[CH:6]=[CH:7][C:8]([O:15][CH3:16])=[C:9]([C:11]([CH2:12][CH3:13])=[CH:25][CH:26]=[CH:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:10]=1
Reactant: CCC(=O)c1cc(OCOC)ccc1OC
Reactant: CCOC(=O)/C=C/CP(=O)(OCC)OCC
Product: CCOC(=O)C=CC=C(CC)c1cc(OCOC)ccc1OC

Procedure:
In a manner similar to Example 63(c), by reacting 3.9 g (17 mmol) of 3-(5-methoxymethoxy-2-methoxyphenyl)-3-propanone with 8.7 g (34.8 mmol) of ethyl 4-diethylphosphonocrotonate, ethyl 5-(5-methoxymethoxy-2-methoxyphenyl)hepta-2,4-dienoate is obtained which is converted to ethyl 5-(5-hydroxy-2-methoxyphenyl)hepta-2,4-dienoate with concentrated sulphuric acid in ethanol 800 mg (17%).
Reaction SMILES: [CH2:1]1[C:4]2([CH2:8][CH2:7][CH2:6][NH:5]2)[CH2:3][O:2]1.C(N(CC)CC)C.[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[O:28][C:27]([C:29]([N:31]3[CH2:34][CH:33]([O:35][C:36]4[CH:43]=[CH:42][C:39]([CH:40]=O)=[CH:38][CH:37]=4)[CH2:32]3)=[O:30])=[N:26][N:25]=2)=[CH:20][CH:19]=1.[Na].C([O-])(O)=O.[Na+]>ClCCl>[CH2:3]1[C:4]2([CH2:8][CH2:7][CH2:6][N:5]2[CH2:40][C:39]2[CH:38]=[CH:37][C:36]([O:35][CH:33]3[CH2:34][N:31]([C:29]([C:27]4[O:28][C:24]([C:21]5[CH:22]=[CH:23][C:18]([O:17][CH3:16])=[CH:19][CH:20]=5)=[N:25][N:26]=4)=[O:30])[CH2:32]3)=[CH:43][CH:42]=2)[CH2:1][O:2]1
Reactant: COc1ccc(-c2nnc(C(=O)N3CC(Oc4ccc(C=O)cc4)C3)o2)cc1
Reactant: C1CNC2(C1)COC2
Agent: O=C([O-])O
Agent: [Na+]
Agent: [Na]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc(-c2nnc(C(=O)N3CC(Oc4ccc(CN5CCCC56COC6)cc4)C3)o2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 60.5 %

Procedure:
2-Oxa-5-azaspiro[3.4]octane (0.03 g, 0.26 mmol) was dissolved in dichloromethane (2 ml). Triethylamine (0.04 ml, 0.29 mmol) was added, followed by 4-(1-(5-(4-methoxyphenyl)-1,3,4-oxadiazole-2-carbonyl)azetidin-3-yloxy)benzaldehyde (0.1 g, 0.26 mmol) and finally sodium triacetoxyhydroborate (0.112 g, 0.53 mmol). The mixture was stirred at ambient temperature overnight. The reaction mixture was then diluted with dichloromethane (10 ml) and subsequently shaken with NaHCO3 (sat. 3 ml). The two phases were separated by the use of a phase separator. Evaporation of the organic phase afforded a residue, which was purified by preparative reverse-phase. HPLC at pH 10 to give 0.075 g (60%) of the desired product as a solid. 1H NMR (600 MHz, DMSO) δ 1.62 (dt, 2H), 2.1-2.15 (m, 2H), 2.49 (t, 2H), 3.88 (s, 3H), 3.91 (s, 2H), 4.09 (ddd, 1H), 4.43 (d, 2H), 4.54 (ddd, 1H), 4.63 (ddd, 1H), 4.80 (d, 2H), 5.09 (ddd, 1H), 5.16 (ddd, 1H), 6.86 (d, 2H), 7.17-7.21 (m, 2H), 7.30 (d, 2H), 8-8.04 (m, 2H). MS (APCI+) m/z 477.2 [M+H]+, LC purity: 95%
Reaction SMILES: [CH2:1]([P:9]([CH2:19][CH2:20][CH2:21][CH2:22][C:23]([O:25]C(=O)CCCCP(CCCCCCCC)(CCCCCCCC)=O)=[O:24])([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].P([O-])(OCCCC)(OCCCC)=O.C([Mg]I)CCCCCCC.C(O)(=O)CCC=C>>[CH2:1]([P:9]([CH2:19][CH2:20][CH2:21][CH2:22][C:23]([OH:25])=[O:24])([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: CCCCCCCCP(=O)(CCCCCCCC)CCCCC(=O)OC(=O)CCCCP(=O)(CCCCCCCC)CCCCCCCC
Agent: C=CCCC(=O)O
Agent: CCCCCCCC[Mg]I
Agent: CCCCOP(=O)([O-])OCCCC
Product: CCCCCCCCP(=O)(CCCCCCCC)CCCCC(=O)O

Procedure:
In a similar vein, hybrid dispersing agents were designed for CdSe nanoparticles and in this case, phosphine oxide chain ends were required for interaction with the surface of the CdSe. Using an anhydride functionalization approach requires 5-(dioctylphosphoryl)pentanoic anhydride, 13, which was synthesized by initial alkylation of di-n-butyl phosphate, 14, with octylmagnesium iodide followed by reaction with 4-pentenoic acid using AlBN to give 5-(dioctylphosphoryl)pentanoic acid, 15, which was converted into the desired anhydride, 13, using DCC (See FIG. 9). The anhydride was then used to functionalize the chain ends of 9a to give the phosphine oxide functionalized dendritic-linear copolymer, 16 (See FIG. 10).
Reaction SMILES: [CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:39](O)=[O:40])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]([N:23]4[CH2:28][CH2:27][CH:26]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)[CH2:25][CH2:24]4)=[O:22])=[CH:18][C:17]4[CH:35]=[CH:36][CH:37]=[CH:38][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.[NH2:51][CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][N:54]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>C(Cl)Cl>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:39]([NH:51][CH2:52][C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][N:54]=4)=[O:40])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]([N:23]4[CH2:28][CH2:27][CH:26]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)[CH2:25][CH2:24]4)=[O:22])=[CH:18][C:17]4[CH:35]=[CH:36][CH:37]=[CH:38][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(O)c1ccc2c(C3CCCCC3)c3n(c2c1)CC(C(=O)N1CCC(N2CCOCC2)CC1)=Cc1ccccc1-3
Reactant: NCc1ccccn1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NCc1ccccn1)c1ccc2c(C3CCCCC3)c3n(c2c1)CC(C(=O)N1CCC(N2CCOCC2)CC1)=Cc1ccccc1-3
Temperature: 25 °C
Reaction time: 22 h
Yield: 51.4 %

Procedure:
To a stirred solution of 13-cyclohexyl-6-[[4-(4-morpholinyl)-1 -piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid (70 mg, 0.13 mmol) in CH2Cl2 (1 mL) were added N,N-diisopropylethylamine (85 μL, 0.49 mmol), 2-(aminomethyl)pyridine (17 mg, 0.16 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (34 mg, 0.18 mmol), and 1 -hydroxybenzotriazole (24 mg, 0.18 mmol). The suspension was allowed to stir at r.t. for 22 hr, filtered through Celite, and chromatographed on silica gel (gradient elution: 0%→15% MeOH in CH2Cl2) to afford the title compound as a yellow solid (43 mg, 51% yield). LC/MS (ESI) retention time: 1.57 min, m/z 643 (MH+); 1H NMR (400 MHz, CDCl3) δ 1.15-1.27 (m, 3 H) 1.29-1.45 (m, 3 H) 1.48-1.58 (m, 1 H) 1.61-1.70 (m, 1 H) 1.71-1.81 (m, 2 H) 1.86-1.97 (m, 1 H) 1.98-2.15 (m, 3 H) 2.27 (t, J=11.08 Hz, 1 H) 2.38 (s, 4 H) 2.60-2.77 (m, 2 H) 2.78-2.89 (m, 1 H) 3.61 (s, 4 H) 4.40 (s, 1 H) 4.79 (d, J=4.53 Hz, 2 H) 5.09 (s, 1 H) 6.81 (s, 1 H) 7.18-7.22 (m, 1 H) 7.36 (t, J=8.18 Hz, 2 H) 7.41-7.49 (m, 2 H) 7.50-7.59 (m, 2 H) 7.62-7.73 (m, 2 H) 7.89 (d, J=8.56 Hz, 1 H) 8.05 (s, 1 H) 8.56 (d, J=4.53 Hz, 1 H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([CH:13]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:7]=[CH:6]2.[H-].[Na+].CI.[C:28](O)(=O)C(O)=O>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([C:13]([CH3:28])([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:7]=[CH:6]2
Reactant: CCOC(=O)C(C(=O)OCC)c1ccc2cc(OC)ccc2c1
Reactant: O=C(O)C(=O)O
Agent: [H-]
Agent: [Na+]
Solvent: CO
Solvent: CI
Product: CCOC(=O)C(C)(C(=O)OCC)c1ccc2cc(OC)ccc2c1

Procedure:
A mixture of 31.6 g. of diethyl 6-methoxy-2-naphthylmalonate, 2.4 g. of sodium hydride, and 350 ml. of methanol is stirred for one hour; then 24 g. of methyliodide are added and the resulting mixture is refluxed for 2 hours. The cooled mixture is neutralized with aqueous oxalic acid. The product, diethyl 6-methoxy-2-naphthyl-α-methylmalonate, is isolated, hydrolyzed, and decarboxylated by the means of the above described processes to give 6-methoxy-2-naphthyl-α-methylacetic acid.
Reaction SMILES: [CH2:1]([C:3]1[CH:11]=[C:10]([CH2:12][CH3:13])[C:9](I)=[CH:8][C:4]=1[C:5]([OH:7])=[O:6])[CH3:2].[Li]CCCC.Cl[C:21]([O:23][CH3:24])=[O:22]>O1CCCC1>[CH2:1]([C:3]1[CH:11]=[C:10]([CH2:12][CH3:13])[C:9]([C:21]([O:23][CH3:24])=[O:22])=[CH:8][C:4]=1[C:5]([OH:7])=[O:6])[CH3:2]
Reactant: CCc1cc(CC)c(C(=O)O)cc1I
Reactant: COC(=O)Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCc1cc(CC)c(C(=O)OC)cc1C(=O)O
Temperature: -78 °C
Reaction time: 0.08 h
Yield: 24.8 %

Procedure:
To a stiffed solution of 2,4-diethyl-5-iodobenzoic acid (compound 204.4., 500 mg, 1.64 mmol, 1.00 equiv, 90%) in tetrahydrofuran (20 mL) at −78° C. under nitrogen was added dropwise a solution of n-BuLi (1.73 mL, 4.10 mmol, 2.36 M in THF). After 5 minutes, a solution of methyl chloroformate (0.315 mL, 4.10 mmol, 2.50 equiv) in THF (5 mL) was added dropwise to the reaction at −78° C. over 5 minutes. The reaction was stirred for another 5 min at −78° C., and then carefully quenched with 10 mL of water. The pH was adjusted to 1-2 with hydrochloric acid (6 M) and the resulting mixture was extracted with ethyl acetate (2×30 mL). The combined organic layers were washed with 20 mL of brine, then dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatograph with ethyl acetate-petroleum ether (1:20) as eluent to yield 96 mg (25%) of the title compound as an off-white solid.