Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([C:7]2[O:11][CH:10]=[N:9][C:8]=2[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[I:27]I.CCOC(C)=O>C1COCC1>[I:27][C:10]1[O:11][C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[C:8]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[N:9]=1
Reactant: CCOC(=O)c1ncoc1-c1ccccc1
Reactant: II
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCOC(=O)c1nc(I)oc1-c1ccccc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 82 %

Procedure:
To a solution of ethyl 5-phenyl-1,3-oxazole-4-carboxylate (Example 29, 0.921 mmol, 1 eq.) in THF (7 mL) at −78° C. was added a solution of lithium bis(trimethylsilyl)amide in THF (1M, 1.11 mmol, 1.2 eq.) dropwise by syringe. The resulting solution was stirred at −78° C. for 1 hour at which time a solution of iodine (1.38 mmol, 1.5 eq. in 2 mL THF) was added dropwise by a syringe. The reaction mixture was allowed to warm to room temperature and stirred at this temperature for 1.5 hours. The resulting solution was poured onto 10% aqueous NaS2O3 (15 mL) and extracted with ethyl acetate. The organic extracts were washed with brine, dried over anhydrous sodium sulfate, concentrated in vacuo and purified by medium pressure column chromatography (Biotage 40S normal phase silica gel column, hexanes:EtOAc=9:1). The product was obtained as a pale yellow solid in 82% yield. MH+=344.0, Rf=0.31 (hexanes:EtOAc=6:1), retention time (LC-MS)=3.01 min.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][N:3]=1.C[C:10]([O-:12])=[O:11].[Na+].ClCCl.[CH2:17](O)[CH3:18]>>[F:8][C:5]1[CH:6]=[CH:7][C:2]([C:10]([O:12][CH2:17][CH3:18])=[O:11])=[N:3][CH:4]=1
Reactant: Fc1ccc(Br)nc1
Reactant: CCO
Reactant: CC(=O)[O-]
Agent: [Na+]
Solvent: ClCCl
Product: CCOC(=O)c1ccc(F)cn1
Temperature: 90 °C
Yield: 68.6 %

Procedure:
To a Parr shaker add 2-bromo-5-fluoropyridine (Example 382, Part A) (7.00 g, 39.8 mmol), NaOAc (13.1 g, 159 mmol), absolute ethanol (100 mL) and [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(ll):dichloromethane (1.62 g, 1.99 mmol). Charge the reaction vessel with 50 psi of CO. Heat at 90° C. for 18.25 hours. Cool the reaction mixture before filtering through a Celite® pad. Wash the pad with ethyl acetate, then concentrate the filtrate. Purify by flash chromatography, eluting with 25% ethyl acetate in hexanes to give the title compound (4.62 g, 68.6%): MS ES+ 169.9 (M+H)+, base peak MS ES+ 141.8 (M+H—CH2CH3)+; HPLC [YMC-Pack Pro C-18 (150×4.6 mm, S-5 microm), 0.1% TFA/acetonitrile in 0.10% TFA/water at 1.0 mL/min, 5-95% over 19 min], tR=10.3 min, 97.0 purity.
Reaction SMILES: [C:1]([C:4]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:10]2[C:5]=1[CH:6]=[CH:7][C:8](=[O:22])[NH:9]2)(=[O:3])[CH3:2].[Br-:23].[Br-].[Br-].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>O1CCCC1>[CH2:15]([O:14][C:11]1[CH:12]=[CH:13][C:4]([C:1](=[O:3])[CH2:2][Br:23])=[C:5]2[C:10]=1[NH:9][C:8](=[O:22])[CH:7]=[CH:6]2)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CC(=O)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Reactant: [Br-]
Agent: c1cc[nH+]cc1
Solvent: C1CCOC1
Product: O=C(CBr)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Temperature: 0 °C
Yield: 81.9 %

Procedure:
5-Acetyl-8-benzyloxy-1H-quinolin-2-one (372 g, 1.27 mol) was dissolved in tetrahydrofuran (3.6 L) and the solution was cooled to 0° C. Pyridinium tribromide (453 g, 1.27 mol) was added thereto in portions, and the mixture was heated under reflux for 3 hours. Thereafter, tetrahydrofuran (3.1 L) was added and the mixture was heated under reflux overnight. The precipitate was collected by filtration and washed with tetrahydrofuran. The solid was suspension-washed with tetrahydrofuran (2.3 L) and, thereafter, washed with purified water (3 L). Separately, the tetrahydrofuran filtrate and the washings were mixed, concentrated under reduced pressure, and the residue was suspension-washed with tetrahydrofuran (1 L). The solids were combined and dried under reduced pressure to obtain 8-benzyloxy-5-(2-bromoacetyl)-1H-quinolin-2-one (387 g).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[CH:5]=[C:4]([C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH:16]=[CH:15][CH:14]=2)[N:3]=1.[CH3:23][N:24]([CH3:29])[CH:25](NC)[CH3:26].C(=O)([O-])[O-].[K+].[K+].[CH3:36][N:37](C=O)C>O>[CH3:29][N:24]([CH3:23])[CH2:25][CH2:26][N:37]([CH3:36])[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[CH:5]=[C:4]([C:13]2[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH:16]=[CH:15][CH:14]=2)[N:3]=1
Reactant: CNC(C)N(C)C
Reactant: Cc1ccc2cc(-c3cccc4ccccc34)nc(Cl)c2c1
Reactant: CN(C)C=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: Cc1ccc2cc(-c3cccc4ccccc34)nc(N(C)CCN(C)C)c2c1
Temperature: 25 °C
Yield: 86 %

Procedure:
A mixture of the product of Example 31, Part A, 1-chloro-7-methyl-3-(1-naphthalenyl)-isoquinoline (2.00 g, 6.58 mmol), N,N,N'-trimethylethanediamine (1.7 mL, 13.4 mmol), and potassium carbonate (2.75 g, 19.9 mmol) in DMF (5 mL) was refluxed overnight. The reaction mixture was cooled to room temperature, diluted with water, and extracted with methylene chloride. The combined organic extracts were washed with water, dried, and concentrated. The residue was purified by flash chromatography with 1:1 hexane-ethyl acetate to afford the title compound (2.08 g, 5.63 mmol, 86% yield) as an oil: IR(CHCl3) 3052, 1591 cm-1 ; MS m/e 370(M+ +H); 1H NMR(CDCl3) δ 8.23-8.37(m,1H), 8.03(s,1H), 7.80-7.97(m,2H), 7.63-7.79(m,2H), 7.33-7.62(m,5H), 3.62(t,J=7 Hz,2H), 3.13(s,3H), 2.80(t,J=7 Hz,2H), 2.60(s,3H), 2.30(s,6H).
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][CH:2]1[CH2:11][N:12]1[CH2:16][CH2:15][C:14]([CH2:18][OH:19])([CH3:17])[CH2:13]1.[H-].[Na+].I[CH3:23].O>O1CCCC1>[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][CH:2]1[CH2:11][N:12]1[CH2:16][CH2:15][C:14]([CH2:18][O:19][CH3:23])([CH3:17])[CH2:13]1
Reactant: CI
Reactant: CC1(CO)CCN(CC2COc3ccccc3O2)C1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: COCC1(C)CCN(CC2COc3ccccc3O2)C1
Temperature: 60 °C
Reaction time: 2 h

Procedure:
A solution of 56 mg (0.21 mmol) of [1-(2,3-Dihydro-benzo[1,4]dioxin-2-ylmethyl)-3-methyl-pyrrolidin-3-yl]-methanol in 1.5 ml of tetrahydrofuran was added to a flask containing 58 mg (2.40 mmol) of sodium hydride, previously washed with heptane under argon. The reaction mixture was stirred at 60° C. for 2 h, cooled to 0° C. followed by dropwise addition of a solution containing 16 μl (0.25 mmol) of iodomethane in tetrahydrofuran (0.5 ml). The reaction mixture was allowed to warm to room temperature and the stirring was continued for 1½ h. Water was slowly added and tetrahydrofuran was evaporated off and the water phase was extracted with dichloromethane (3×25 ml). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and evaporated to dryness. Purification by column chromatography (silica gel, ethyl acetate/heptane, 7:13) yielded the desired pure methyl ether.
Reaction SMILES: [OH:1][C:2]1[NH:7][C:6](=[O:8])[N:5]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:4](=[O:16])[C:3]=1[C:17]([NH:19][CH2:20][C:21]([O:23]CC)=[O:22])=[O:18].[F:26][C:27]([F:37])([F:36])[C:28]1[CH:35]=[CH:34][C:31]([CH2:32]Br)=[CH:30][CH:29]=1.C(=O)([O-])[O-].[Na+].[Na+].Cl>CN(C)C=O>[OH:1][C:2]1[N:7]([CH2:32][C:31]2[CH:34]=[CH:35][C:28]([C:27]([F:37])([F:36])[F:26])=[CH:29][CH:30]=2)[C:6](=[O:8])[N:5]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:4](=[O:16])[C:3]=1[C:17]([NH:19][CH2:20][C:21]([OH:23])=[O:22])=[O:18]
Reactant: FC(F)(F)c1ccc(CBr)cc1
Reactant: CCOC(=O)CNC(=O)c1c(O)[nH]c(=O)n(Cc2ccccc2)c1=O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C(O)CNC(=O)c1c(O)n(Cc2ccc(C(F)(F)F)cc2)c(=O)n(Cc2ccccc2)c1=O
Temperature: 100 °C
Reaction time: 2.5 h
Yield: 30.5 %

Procedure:
A mixture of ethyl N-{[6-hydroxy-2,4-dioxo-3-(phenylmethyl)-1,2,3,4-tetrahydro-5-pyrimidinyl]carbonyl}glycinate (example 11a, 356 mg, 1.03 mmoles), 4-trifluoromethylbenzyl bromide (175 uL, 1.13 mmoles) and sodium carbonate (330 mg, 3.1 mmoles) in dimethylformamide (6.0 mL) was stirred under argon at 100° C. for 2.5 hours. The mixture was cooled, poured into 1 molar hydrochloric acid and extracted with ethyl acetate (×2). The ester was hydrolysed by stirring in a mixture of ethanol (3 mL) and 1 molar sodium hydroxide solution (3 mL) for 3 hours. The mixture was acidified and extracted with ethyl acetate. Purification by preparative HPLC (acetonitrile-water—0.1% TFA, 20-100%) and crystallization from ethanol-water gave the title compound (150 mg, 30%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.12 (s, 1 H), 10.12 (t, J=5.56 Hz, 1 H), 7.69 (d, J=8.08 Hz, 2 H), 7.53 (d, J=8.08 Hz, 2 H), 7.24-7.35 (m, 5 H), 5.11 (s, 2 H), 5.03 (s, 2 H), 4.14 (d, J=5.81 Hz, 2 H).
Reaction SMILES: [CH2:1]([C:18]([OH:20])=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16].[CH2:21](O)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[C:29]1([CH3:39])[CH:34]=[CH:33][C:32](S(O)(=O)=O)=[CH:31][CH:30]=1>C1(C)C=CC=CC=1>[CH2:21]([O:16][C:15]([CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH2:1][C:18]([O:20][CH2:39][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:19])=[O:17])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: O=C(O)CCCCCCCCCCCCCCC(=O)O
Reactant: OCc1ccccc1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: O=C(CCCCCCCCCCCCCCC(=O)OCc1ccccc1)OCc1ccccc1

Procedure:
A method of synthesis for a compound obtained by converting one terminal of 1,14-tetradecane dicarboxylic acid into a benzyl ester is described. The compound can be synthesized by using Japanese Patent Application Public Disclosure (Kokai) Hei 04-18245 or “Organic Synthesis II” pages 276-277 as references. That is, 5 g (17.5 millimoles) of 1,14-tetradecane dicarboxylic acid, 8.37 g of benzyl alcohol, 50 ml of toluene and para-toluene sulfonic acid were placed in a flask and were allowed to reflux while using a Dean Stark dehydration device to remove water. After eight hours of refluxing, about one milliliter of water had been removed. The reaction solution was dissolved in hexane and washed using a saturated sodium bicarbonate solution first and water second. The organic phase was dried using sodium sulfate, and the solvent was removed using reduced pressure distillation. The product was recrystallized using hexane, and 8.1 g of 1,14-tetradecane dicarboxylic acid dibenzyl ester was obtained. Next, 4.8 g (16.7 millimoles) of 1,14-tetradecane dicarboxylic acid, 1.8 g of benzyl alcohol, 50 ml of toluene and sulfuric acid were freshly added to 5.97 g (12.8 millimoles) of this 1,14-tetradecane dicarboxylic acid dibenzyl ester, and the mixture was heated and allowed to reflux for five hours. The reaction mixture was subsequently dissolved in 300 ml of isopropanol/chloroform (1/5 volumetric ratio), and the solution was washed with water and dried using sodium sulfate. The solution was concentrated under reduced pressure and recrystallized using a mixed solvent of ether/hexane (1/4 volumetric ratio) to obtain 3.77 g (10.1 millimoles) of 1,14-tetradecane dicarboxylic acid monobenzyl ester.
Reaction SMILES: Br[C:2]1[N:7]=[CH:6][C:5]([N:8]2[CH2:12][C:11]([CH3:14])([CH3:13])[N:10]([CH3:15])[C:9]2=[O:16])=[CH:4][CH:3]=1.[C:17]1([C:23]#[CH:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(N(CC)CC)C>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:15][N:10]1[C:11]([CH3:14])([CH3:13])[CH2:12][N:8]([C:5]2[CH:6]=[N:7][C:2]([C:24]#[C:23][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:3][CH:4]=2)[C:9]1=[O:16]
Reactant: C#Cc1ccccc1
Reactant: CN1C(=O)N(c2ccc(Br)nc2)CC1(C)C
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CN1C(=O)N(c2ccc(C#Cc3ccccc3)nc2)CC1(C)C
Temperature: 90 °C
Reaction time: 4 h
Yield: 60.4 %

Procedure:
Bis-(triphenylphosphine)-palladium(II)dichloride (6 mg, 8.5 μmol, 0.03 equiv.) was dissolved in 1 ml DMF. (80 mg, 282 μmol) 1-(6-Bromo-pyridin-3-yl)-3,4,4-trimethyl-imidazolidin-2-one (E ample 3, step 2) and phenylacetylene (58 mg, 563 μmol, 2 equiv.) were added at room temperature. Triethylamine (118 μl 0.845 mmol, 3 equiv.), triphenylphosphine (4.4 mg, 16.9 μmol, 0.06 equiv.) and copper(I)iodide (1.6 mg, 8.45 μmol, 0.03 equiv.) were added and the mixture was stirred for 4 hours at 90° C. The reaction mixture was evaporated to dryness with Isolute® and the crude product was purified by flash chromatography by directly loading the solid onto a silica gel column and eluting with an ethyl acetate: heptane gradient 0:100 to 100:0. The desired 3,4,4-trimethyl-1-(6-phenylethynyl-pyridin-3-yl)-imidazolidin-2-one (52 mg, 61% yield) was obtained as a yellow solid, MS: m/e=306.2 (M+H+).
Reaction SMILES: [CH3:1][C:2]1[N:3]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[C:4](=[O:7])[NH:5][N:6]=1.[H-].[Na+].[CH2:16]([CH:18]1[O:20][CH2:19]1)Br.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C(Cl)(Cl)Cl.C(OCC)(=O)C>[CH3:1][C:2]1[N:3]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[C:4](=[O:7])[N:5]([CH2:16][CH:18]2[CH2:19][O:20]2)[N:6]=1
Reactant: Cc1n[nH]c(=O)n1-c1cccnc1
Reactant: BrCC1CO1
Agent: O=C([O-])[O-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: ClC(Cl)Cl
Product: Cc1nn(CC2CO2)c(=O)n1-c1cccnc1
Temperature: 25 °C

Procedure:
After dissolving 5-methyl-4-pyridin-3-yl-2,4-dihydro[1,2,4]triazol-3-one (CAS 79369-46-3) (100 mg) in N,N-dimethylformamide (2 ml), sodium hydride (60% in oil) (27 mg) was added and the mixture was stirred at room temperature. Epibromohydrin (73 μl) was then added and the mixture was stirred overnight at room temperature. A saturated aqueous solution of sodium carbonate was added to the reaction mixture, and extraction was performed with ethyl acetate and chloroform. The extract was dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (136 mg).
Reaction SMILES: [O:1]1[CH2:3][C@H:2]1[CH2:4][O:5][C:6]1[C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[NH:11][C:10]=2[CH:9]=[CH:8][CH:7]=1.ClC1C=CC=C(C(OO)=[O:27])C=1>C(Cl)Cl>[OH:27][C:7]1[CH:8]=[CH:9][C:10]2[NH:11][C:12]3[C:17]([C:18]=2[C:6]=1[O:5][CH2:4][C@@H:2]1[CH2:3][O:1]1)=[CH:16][CH:15]=[CH:14][CH:13]=3
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: c1ccc2c(c1)[nH]c1cccc(OC[C@@H]3CO3)c12
Solvent: ClCCl
Product: Oc1ccc2[nH]c3ccccc3c2c1OC[C@@H]1CO1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 20.6 %

Procedure:
A solution of 4-[(2S)-oxiranylmethoxy]-9H-carbazole (0.183 g, 0.76 mmol) in 20 mL dry methylene chloride was treated with 0.258 g of 56-86% m-chloroperbenzoic acid. The reaction was stirred at ambient temperature for 45 minutes. The reaction mixture was partitioned with saturated sodium bicarbonate (sat'd NaHCO3) The organic phase was dried (Na2SO4) and concentrated to a dark red oil. Purification by flash chromatography eluting with methylene chloride (CH2Cl2), afforded 0.040 g of the title compound.
Reaction SMILES: [CH2:1]1C[O:4][CH2:3][CH2:2]1.C(Cl)(=O)C=C.[NH2:11][CH:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH2:13]1.O>C(OCC)(=O)C>[CH:12]1([NH:11][C:3](=[O:4])[CH:2]=[CH2:1])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH2:13]1
Reactant: NC1CCc2ccccc21
Reactant: C1CCOC1
Agent: C=CC(=O)Cl
Solvent: CCOC(C)=O
Solvent: O
Product: C=CC(=O)NC1CCc2ccccc21
Reaction time: 0.33 h

Procedure:
A THF (10 mL) solution of acrylic acid chloride (2.04 g) was added dropwise to a THF (30 mL) solution of 1-aminoindane (3.00 g) and TEA (2.28 g) under ice-cooling, and the reaction solution was agitated for 20 minutes at the temperature. Water and ethyl acetate were added to this reaction mixture, and the organic layer was partitioned. The organic layer was washed with a saturated saline solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. 2.23 g of the title compound was obtained by adding ether to the residue and filtering insoluble matter.
Reaction SMILES: C([N-]C(C)C)(C)C.[Li+].C(NC(C)C)(C)C.C([Li])CCC.[CH:21]1([CH2:27][CH:28]2[CH2:33][CH2:32][O:31][C:29]2=[O:30])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.[CH2:34]([O:36][CH2:37]Cl)[CH3:35]>C1COCC1>[CH:21]1([CH2:27][C:28]2([CH2:37][O:36][CH2:34][CH3:35])[CH2:33][CH2:32][O:31][C:29]2=[O:30])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]1
Reactant: CCOCCl
Reactant: O=C1OCCC1CC1CCCCC1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: CCOCC1(CC2CCCCC2)CCOC1=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 64.3 %

Procedure:
A solution of lithium diisopropylamide prepared from diisopropylamine (6.50 mL) and butyllithium (29.0 mL of 1.6M solution in hexanes) in THF (105 mL) was treated dropwise with 2-(cyclohexyl-methyl)-γ-butyrolactone (6.96 g) at −78° C. The reaction mixture was stirred at the same temperature for additional 30 min and then treated dropwise with chloromethyl ethyl ether (5.05 g). Upon completion of the addition, the mixture was allowed to slowly warm-up to room temperature and stirred at this temperature overnight. After that, the mixture was quenched by pouring onto a mixture of ice and 10% aqueous phosphoric acid. The formed organic phase was separated and the aqueous phase was extracted with toluene. The combined organic phases were washed with water, dried over potassium sulfate, filtered, concentrated on a rotary evaporator and purified by column chromatography (silica gel, eluent-hexane) to give 5.90 g (64%) of the title compound.
Reaction SMILES: [OH:1][C:2]([CH3:25])([CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH:3]=[CH:4][C@@H:5]1[CH2:9][CH2:8][C:7](=[O:10])[C@H:6]1[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([OH:19])=[O:18].[CH3:26]O>>[OH:1][C:2]([CH3:25])([CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH:3]=[CH:4][C@@H:5]1[CH2:9][CH2:8][C:7](=[O:10])[C@H:6]1[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([O:19][CH3:26])=[O:18]
Reactant: CO
Reactant: CCCCCC(C)(O)C=C[C@@H]1CCC(=O)[C@H]1CCCCCCC(=O)O
Product: CCCCCC(C)(O)C=C[C@@H]1CCC(=O)[C@H]1CCCCCCC(=O)OC

Procedure:
In the same manner but using the appropriate choice of the compound of formula 1 and lower alkanol, other corresponding esters of formula 1 (R1 = lower alkyl) are prepared; for example, the corresponding lower alkyl esters of the products of Table IV. More specifically exemplified, the choice of trans-7-[2-(3-hydroxy-3-methyl-1-octenyl)-5-oxocyclopentyl]heptanoic acid, described in Example 68, as the compound of formula 1 and methanol as the lower alkanol in the procedure of this example give methyl trans-7-[2-(3-hydroxy-3-methyl-1-octenyl)5-oxocyclopentyl]heptanoate, γmax film 3475, 1730 cm-1, nmr (CDCl3) δ 0.89 (t, 3H), 3.64 (s, 3H), 5.61 (m, 2H).
Reaction SMILES: [OH-].[K+].C([S:6][CH2:7][CH2:8][C:9]([N:11]1[CH:16]([C:17]([O:19]CC2C=CC=CC=2)=[O:18])[CH2:15][S:14][C:13]([CH:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)=[N:12]1)=[O:10])(=O)C.C(O)(=O)C>CO.O>[CH:27]1([C:13]2[S:14][CH2:15][CH:16]([C:17]([OH:19])=[O:18])[N:11]([C:9](=[O:10])[CH2:8][CH2:7][SH:6])[N:12]=2)[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]1
Reactant: CC(=O)SCCC(=O)N1N=C(C2CCCCC2)SCC1C(=O)OCc1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CO
Solvent: O
Product: O=C(O)C1CSC(C2CCCCC2)=NN1C(=O)CCS
Reaction time: 2 h
Yield: 39.1 %

Procedure:
1M Potassium hydroxide solution in methanol (5.83 ml) was added to a solution of the product of step (b) (0.87 g) in methanol (10 ml) and water (5 ml). The mixture was stirred under an atmosphere of nitrogen for 2 hours. Acetic acid was added and the solvent evaporated under reduced pressure. The mixture was purified by flash chromatography using 1% acetic acid/ethyl acetate as eluent to yield the title compound (0.24 g) as a white solid. mp 95°-97°.
Reaction SMILES: [OH-].[Na+].[CH:3]([N:6]1[CH2:13][CH:12]2[CH2:14][CH:8]([CH2:9][NH:10][CH2:11]2)[CH2:7]1)([CH3:5])[CH3:4].[C:15](Cl)(=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.O>C(Cl)Cl.C(OCC)(=O)C>[C:15]([N:10]1[CH2:11][CH:12]2[CH2:14][CH:8]([CH2:7][N:6]([CH:3]([CH3:5])[CH3:4])[CH2:13]2)[CH2:9]1)(=[O:22])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: CC(C)N1CC2CNCC(C2)C1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: O
Product: CC(C)N1CC2CC(CN(C(=O)c3ccccc3)C2)C1
Temperature: 25 °C
Reaction time: 2.75 h
Yield: 82.4 %

Procedure:
A three-necked, 50-mL, round-bottomed flask was equipped with a magnetic stirrer, an ice bath, a standard condenser with a N2 inlet, and two glass stoppers. To a solution of 10% NaOH (8.94 g, 22.3 mmol) was added the amine (31, 1.14 g, 6.77 mmol) in CH2Cl2 (15 mL) in one portion. Dropwise addition of a solution of benzoyl chloride (1.05 g, 7.45 mmol) in CH2Cl2 (5 mL) to the mixture over 15 min under N2 was followed by stirring an additional 2.75 h at RT. After the addition of H2O (30 mL), the organic layer was separated. Additional extracts (CH2Cl2, 3×25 mL) were combined with the initial organic layer, dried (Na2SO4, 1 h), filtered, and concentrated (aspirator followed by vacuum pump, 1 h, RT/0.2 mm Hg) to give an orange oil. Chromatography of the oil was performed over neutral alumina (200 g, 2.1 cm×33 cm) with ethyl acetate as eluant. Fractions (Rf =0.70) were combined and concentrated (rotary evaporator then vacuum pump, overnight, RT/0.2 mm Hg) to yield 1.52 g (82.4%) of the amide (32) as an oil which was used without further purification. IR (film) cm-1 3085, 3065, 3035 (Ar C--H), 2970, 2925, 2865, 2805, 2780, 2750 (C--H), 1635 (C=O), 730, 710 (C--H out of plane, mono); 1H NMR (DCCl3) δ0.96 (d, 3H, CH3, J=6.4 Hz), 1.07 (d, 3H, CH3, J=6.6 Hz), 1.65-1.78, [m, 3H, H(5) and H(9)], 1.97 [bs, 1H, H(1)], 2.41 [d, 1H, H(4)ax, J=10.3 Hz], 2.50 [d, 1H, H(6)ax, J=11.0 Hz] , 2.62 [m, 1H, CH(CH3)2, J=6.5 Hz], 2.72 [d, 1H, H(6)eq, J=10.6 Hz], 3.04-3.07 [m, 2H, H(2)ax and H(4)eq ], 3.30 [d, 1H, H(8)ax, J=13.2 Hz], 3.74 [d, 1H, H(8)eq, J=12.8 Hz], 4.77 [d, 1H, H(2)eq, J=13.9 Hz], 7.28-7.41 (m, 5H, Ar--H); 13C NMR (DCCl3) ppm 16.30 (CH3), 19.33 (CH3), 29.06 [C(1)], 29.76 [C(5)], 32.29 [C(9)], 46.55 [C(2)], 52.19 [C(4)], 52.62 [C(8)], 54.34 [CH(CH3 )2 ], 54.75 [C(6)], 126.75, 128.24, 128.67, 137.75 (Ar--C), 170.09 (C=O).
Reaction SMILES: [CH2:1]([C:14](O)=O)[CH2:2][C:3]([O:5][O:6][C:7]([CH2:9][CH2:10][C:11](O)=O)=[O:8])=[O:4].[C:17](OOC(C1C=CC=CC=1)(C)C)(C1C=CC=CC=1)([CH3:19])[CH3:18].[C:37](OOC(C)(C)C)(C)([CH3:39])[CH3:38]>>[C:7]([O:6][O:5][C:3](=[O:4])[C:2]1[CH:1]=[CH:14][CH:39]=[CH:37][CH:38]=1)(=[O:8])[C:9]1[CH:10]=[CH:11][CH:19]=[CH:17][CH:18]=1
Reactant: CC(C)(OOC(C)(C)c1ccccc1)c1ccccc1
Reactant: O=C(O)CCC(=O)OOC(=O)CCC(=O)O
Reactant: CC(C)(C)OOC(C)(C)C
Product: O=C(OOC(=O)c1ccccc1)c1ccccc1

Procedure:
succinic acid peroxide, dicumyl peroxide; di-tert-butyl peroxide;