Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.N1CCC[C@H]1C(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[CH:33]=[C:34]([C:39]1[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=1)[C:35]([CH3:38])([CH3:37])[CH3:36]>CN(C=O)C.[Cu]I>[CH3:36][C:35]([CH3:38])([CH3:37])/[C:34](/[C:39]1[CH:40]=[CH:41][N:42]=[CH:43][CH:44]=1)=[CH:33]\[N:6]1[C:7]2[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=2[C:4]2[CH2:3][N:2]([CH3:1])[CH2:15][CH2:14][C:5]1=2
Reactant: CC(C)(C)C(=CBr)c1ccncc1
Reactant: Cc1ccc2[nH]c3c(c2c1)CN(C)CC3
Agent: [Cu]I
Agent: O=C(O)[C@@H]1CCCN1
Agent: O=P([O-])([O-])[O-]
Solvent: CN(C)C=O
Product: Cc1ccc2c(c1)c1c(n2/C=C(/c2ccncc2)C(C)(C)C)CCN(C)C1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
2,3,4,5-Tetrahydro-2,8-dimethyl-1H-pyrido[4,3-b]indole (30 mg, 0.15 mmol) was dissolved in DMF. Copper (I) iodide, L-proline (4 mg, 0.03 mmol) and potassium phosphate (63 mg, 0.29 mmol) were added and the reaction mixture was stirred for 10 min. at RT. 4-(1-bromo-3,3-dimethylbut-1-en-2-yl)pyridine (43 mg, 0.18 mmol) was added dropwise and the reaction mixture was purged with nitrogen. The reaction mixture was heated overnight at 85° C. (prolonged heating in some cases was required). DMF was evaporated under reduced pressure, the residue was diluted with water and the solid was filtered. The solid material was purified by silica gel chromatography (100-200 mesh) eluting with 0-7% MeOH-DCM. The product was further purified by HPLC. 1H NMR (CD3OD, freebase) δ (ppm): 8.21 (d, 2H), 7.15 (m, 3H), 7.05 (s, 1H), 6.94 (d, 1H), 6.80 (s, 1H), 3.90 (s, 2H), 3.18 (t, 2H), 2.90 (t, 2H), 2.70 (s, 3H), 2.36 (s, 3H), 1.30 (s, 9H).
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2[CH:33]=[CH:32][C:14]([O:15][C:16]3[CH:25]=[C:24]4[C:19]([CH:20]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:21][CH2:22][O:23]4)=[CH:18][C:17]=3[Cl:31])=[CH:13][CH:12]=2)=[O:10])[CH:5]=[CH:4][CH:3]=1.[Br-].[C:35]([Zn+])([CH3:38])([CH3:37])[CH3:36]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:35]([C:2]1[N:7]=[C:6]([NH:8][C:9]([C:11]2[CH:12]=[CH:13][C:14]([O:15][C:16]3[CH:25]=[C:24]4[C:19]([CH:20]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:21][CH2:22][O:23]4)=[CH:18][C:17]=3[Cl:31])=[CH:32][CH:33]=2)=[O:10])[CH:5]=[CH:4][CH:3]=1)([CH3:38])([CH3:37])[CH3:36]
Reactant: CC(C)(C)[Zn+]
Reactant: CCOC(=O)C1CCOc2cc(Oc3ccc(C(=O)Nc4cccc(Br)n4)cc3)c(Cl)cc21
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: [Br-]
Product: CCOC(=O)C1CCOc2cc(Oc3ccc(C(=O)Nc4cccc(C(C)(C)C)n4)cc3)c(Cl)cc21
Reaction time: 1 h
Yield: 28.6 %

Procedure:
Ethyl 7-(4-(6-bromopyridin-2-ylcarbamoyl)phenoxy)-6-chlorochroman-4-carboxylate (Example 52, Step A; 30 mg, 0.056 mmol) and bis(tri-t-butylphosphine)palladium (0) (14 mg, 0.028 mmol) were diluted with tert-butylzinc bromide (113 μl, 0.056 mmol) and stirred for 1 hour. The reaction was loaded onto silica gel and eluted with 5% ethyl acetate/hexanes to 70% ethyl acetate/hexanes to yield the desired compound (8 mg, 0.016 mmol, 56% yield).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([OH:10])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].O[CH:12]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[N+:1]([C:4]1[CH:5]=[C:6]([CH:7]=[CH:8][CH:9]=1)[O:10][CH:16]1[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:15]1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1cccc(O)c1
Reactant: CC(C)(C)OC(=O)N1CCC(O)C1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(Oc2cccc([N+](=O)[O-])c2)C1
Temperature: 25 °C
Reaction time: 18 h
Yield: 98.3 %

Procedure:
To a mixture of 3-nitrophenol (4.0 g, 28.8 mmol), tert-butyl 3-hydroxypyrrolidine-1-carboxylate (5.94 g, 31.7 mmol), PPh3 (8.3 g, 31.7 mmol) in THF (40 mL) at 0° C. over argon was added DEAD (5.52 g, 31.7 mmol). The reaction was warmed to room temperature and stirred for 18 hours. The reaction mixture was concentrated and purified by column chromatography to obtain tert-butyl 3-(3-nitrophenoxy)pyrrolidine-1-carboxylate (8.73 g, 98% yield)
Reaction SMILES: [Cl:1][C:2]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:3]=1[CH2:4][N:5]1[C:17]2[CH:16]=[N:15][C:14]([CH2:18][OH:19])=[CH:13][C:12]=2[C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2.[CH:25]1([C:28](Cl)=[O:29])[CH2:27][CH2:26]1>C(Cl)Cl.CCOCC>[CH:25]1([C:28]([O:19][CH2:18][C:14]2[N:15]=[CH:16][C:17]3[N:5]([CH2:4][C:3]4[CH:20]=[C:21]([Cl:24])[CH:22]=[CH:23][C:2]=4[Cl:1])[C:6]4[C:11]([C:12]=3[CH:13]=2)=[CH:10][CH:9]=[CH:8][CH:7]=4)=[O:29])[CH2:27][CH2:26]1
Reactant: O=C(Cl)C1CC1
Reactant: OCc1cc2c3ccccc3n(Cc3cc(Cl)ccc3Cl)c2cn1
Solvent: ClCCl
Solvent: CCOCC
Product: O=C(OCc1cc2c3ccccc3n(Cc3cc(Cl)ccc3Cl)c2cn1)C1CC1
Reaction time: 0.17 h
Yield: 63.5 %

Procedure:
A solution of [9-(2,5-dichlorobenzyl)-9H-β-carbolin-3-yl]methanol (357 mg, 1.0 mmol) and cyclopropyl carbonyl chloride (133 mg, 1.27 mmol) in methylene chloride (5 mL) was allowed to stand for 10 minutes. The solvent was evaporated, and the residue partitioned between aqueous Na2CO3 and methylene chloride. The extract was dried over Na2SO4, filtered and evaporated, affording a resin. This was dissolved in ether and filtered through a plug of silica gel, treated with ethereal hydrogen chloride, evaporated, and the residue recrystallized from ethanol/ethyl acetate/ether, affording 270 mg (58%) of the title compound as a yellow solid. 1H NMR (CDCl3) δ8.85 (s, 1H), 8.44 (s, 1 H), 8.25 (d, J=7.9 Hz, 1H), 7.58 (t, J=7.5 Hz, 1H), 7.35-7.28 (m, 3H), 7.10 (dd, J=8, 2.3 Hz, 1H), 6.37 (d, J=2.3 Hz, 1H), 5.62 (s, 2H), 5.46 (s, 2H), 1.74 (m, 2H), 1.56 (m, 1H), 0.84-0.71 (m, 4H); MS (APCI; (M+H)+) m/z 425.
Reaction SMILES: C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:38])[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C@@H:19]([N:27]3[CH2:32][C@@H:31]([CH3:33])[N:30]([CH2:34][CH:35]=[CH2:36])[CH2:29][C@@H:28]3[CH3:37])[C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=3)[CH:14]=2)[CH2:8][CH2:7]1)=[O:5])C.[OH-].[Na+].Cl.O>C1COCC1.CO>[CH2:34]([N:30]1[C@H:31]([CH3:33])[CH2:32][N:27]([C@@H:19]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=2)[C:15]2[CH:14]=[C:13]([CH:18]=[CH:17][CH:16]=2)[C:12]([N:9]2[CH2:8][CH2:7][CH:6]([C:4]([OH:5])=[O:3])[CH2:11][CH2:10]2)=[O:38])[C@@H:28]([CH3:37])[CH2:29]1)[CH:35]=[CH2:36]
Reactant: C=CCN1C[C@H](C)N([C@@H](c2cccc(O)c2)c2cccc(C(=O)N3CCC(C(=O)OCC)CC3)c2)C[C@H]1C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: C=CCN1C[C@H](C)N([C@@H](c2cccc(O)c2)c2cccc(C(=O)N3CCC(C(=O)O)CC3)c2)C[C@H]1C
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.9 %

Procedure:
To a solution of 1-{3-[(R)-((2S,5R)-4-allyl-2,5-dimethyl-piperazin-1-yl)-(3-hydroxy-phenyl)-methyl]-benzoyl}-piperidine-4-carboxylic acid ethyl ester (512 mg, Example 119) in THF (5 mL) was added 1 N NaOH solution (4 mL). The reaction was stirred at room temperature overnight. The reaction solution was neutralized by the addition of 1 N HCl solution (4 mL). The reaction solution was concentrated to dryness under vacuum to give crude product, which was subjected to reverse phase C-18 column chromatography conducted on CombiFlash™ Sq 16×(gradient: 100% H2O to 100% MeOH) to give 1-{3-[(R)-((2S,5R)-4-allyl-2,5-dimethyl-piperazin-1-yl)-(3-hydroxy-phenyl)-methyl]-benzoyl}-piperidine-4-carboxylic acid (445 mg; 92%). 1H NMR (300 MHz, CD3OD) δ 7.52-7.37 (m, 3H), 7.28 (m, 1H), 7.19 (dd, J=8.0, 8.0 Hz, 1H), 6.72 (m, 3H), 5.93 (m, 1H), 5.45 (m, 2H), 5.30 (s, 1H), 4.48 (m, 1H), 3.69 (m, 2H), 3.39 (m, 1H), 3.19-2.99 (m, 4H), 2.79 (m, 2H), 2.65 (m, 1H), 2.47 (m, 1H), 2.13 (m, 1H), 1.98 (m, 1H), 1.79 (m, 1H), 1.64 (m, 2H), 1.27 (d, J=6.0 Hz, 3H), 1.20 (d, J=6.5 Hz, 3H).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][NH:15][C:16]2[CH:26]=[CH:25][C:19]([C:20]([O:22]CC)=[O:21])=[CH:18][CH:17]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[K+].C(O)C.O.Cl>O>[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][NH:15][C:16]2[CH:17]=[CH:18][C:19]([C:20]([OH:22])=[O:21])=[CH:25][CH:26]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCOC(=O)c1ccc(NCCCCCCCCc2ccccc2)cc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C(O)c1ccc(NCCCCCCCCc2ccccc2)cc1

Procedure:
A mixture of 7 g. of ethyl p-[(8-phenyloctyl)amino]benzoate (prepared as described in Example 32), 7 g. of potassium hydroxide and 100 ml. of ethanol-water (9:1) is refluxed for 3.5 hours. The mixture is acidified while hot with concentrated hydrochloric acid, diluted with water, chilled and filtered. The solid is washed with water to give off-white crystals, m.p. 113°-115° C. Recrystallization from ethanol gives white crystals, m.p. 113°-115° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([OH:8])[CH:7]=1.[CH2:12](Br)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:12]([O:8][C:6]1[CH:7]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=1[N+:9]([O-:11])=[O:10])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=[N+]([O-])c1ccc(Br)cc1O
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: O=[N+]([O-])c1ccc(Br)cc1OCc1ccccc1
Temperature: 25 °C
Yield: 96.5 %

Procedure:
A mixture of 5-bromo-2-nitrophenol (10.4 g, 47.7 mmol), benzyl bromide (9.8 g, 57.2 mmol) and potassium carbonate (9.9 g, 71.5 mmol) was taken up in acetone (50 mL) and heated to reflux for 5 h. After cooling to ambient temperature, the reaction mixture was concentrated in vacuo, diluted with water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The crude material was purified by flash column chromatography (9:1 hexanes/ethyl acetate) to give 2-(benzyloxy)-4-bromo-1-nitrobenzene (14.19 g, 97%) as a light-yellow solid: 1H NMR (CDCl3, 300 MHz) δ 7.76 (d, J=8.4 Hz, 1H), 7.32-7.48 (m, 5H), 7.30 (d, J=1.8 Hz, 1H), 7.19 (dd, J=8.7, 1.8 Hz, 1H), 5.23 (s, 2H).
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]([CH:17]=[CH:18][C:19]=1[O:20][CH3:21])[CH:10]=[C:11]([CH:14]([CH3:16])[CH3:15])[CH:12]=[O:13].C1(P(C2C=CC=CC=2)[C@@H]([C@H](P(C2C=CC=CC=2)C2C=CC=CC=2)C)C)C=CC=CC=1.C(N(CC)CC)C>C1(C)C=CC=CC=1.[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Rh].[Rh].[Rh].[Rh]>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:8]=[C:9]([CH:17]=[CH:18][C:19]=1[O:20][CH3:21])[CH2:10][CH:11]([CH:14]([CH3:16])[CH3:15])[CH:12]=[O:13]
Reactant: COCCCOc1cc(C=C(C=O)C(C)C)ccc1OC
Agent: [Rh]
Agent: C[C@H]([C@@H](C)P(c1ccccc1)c1ccccc1)P(c1ccccc1)c1ccccc1
Agent: [C-]#[O+]
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: COCCCOc1cc(CC(C=O)C(C)C)ccc1OC

Procedure:
A solution of 2-(3-(methoxypropoxy)-4-methoxybenzylidene)-3-methylbutanal (7.0 mmol, 74% E and 26% Z), tetrarhodium dodecacabonyl (0.14 mmol), (2R,3R)-(+)-2,3-Bis-(Diphenylphosphino)butane (R,R-Chiraphos, 0.63 mmol) and 300 ul triethylamine in toluene (75 ml) was transferred into an autoclave. The mixture was hydrogenated at 70-80° C. and 20 bar H2. After 42 hr additional tetrarhodium dodecacarbonyl (0.14 mmol) was added to complete the reaction in 62 hr. The mixture was concentrated to 3.5 g black oil and purified by flash chromatography (heptane/ethyl acetate=2/1). Yield=1.6 g yellow oil (74%).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:3]=1[C:4](Cl)=[O:5].[CH:12]1([CH2:15][CH2:16][NH:17][C:18]([C:20]2[N:21]=[N:22][C:23]([N:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)=[CH:24][CH:25]=2)=[O:19])[CH2:14][CH2:13]1>>[CH:12]1([CH2:15][CH2:16][NH:17][C:18]([C:20]2[N:21]=[N:22][C:23]([N:26]3[CH2:31][CH2:30][N:29]([C:4](=[O:5])[C:3]4[CH:7]=[C:8]([F:11])[CH:9]=[CH:10][C:2]=4[Cl:1])[CH2:28][CH2:27]3)=[CH:24][CH:25]=2)=[O:19])[CH2:14][CH2:13]1
Reactant: O=C(Cl)c1cc(F)ccc1Cl
Reactant: O=C(NCCC1CC1)c1ccc(N2CCNCC2)nn1
Product: O=C(NCCC1CC1)c1ccc(N2CCN(C(=O)c3cc(F)ccc3Cl)CC2)nn1

Procedure:
Following the procedure of Example 3, making variations only as required to use 2-chloro-5-fluorobenzoyl chloride in place of isoxazole-5-carbonyl chloride to react with 6-piperazin-1-yl-pyridazine-3-carboxylic acid (2-cyclopropylethyl)amide, the title compound was obtained as a white solid (94% yield). m.p. 194-196° C. 1H NMR (300 MHz, CDCl3) δ 8.05, 7.96, 7.41-7.37, 7.11-7.03, 7.00, 4.07-3.34, 1.55-1.46, 0.79-0.68, 0.48-0.42, 0.11-0.06. 13C NMR (75 MHz, CDCl3) 6165.7, 163.0, 160.0, 159.7, 145.5, 136.7, 131.5, 127.1, 125.3, 117.8, 115.2, 112.5, 46.0, 44.8, 44.6, 41.2, 39.6, 34.5, 8.6, 4.2. MS (ES+) m/z 432.2 (M+1).
Reaction SMILES: N[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[N+:12]([O-:14])=[O:13])[N:8]([CH2:15][CH3:16])[C:7](=[O:17])[C:6](=[O:18])[NH:5]2.N([O-])=O.[Na+].S(=O)(=O)(O)O>C(O)(=O)C.C(O)C.[Cu-]=O>[CH2:15]([N:8]1[C:9]2[C:4](=[CH:3][CH:2]=[C:11]([N+:12]([O-:14])=[O:13])[CH:10]=2)[NH:5][C:6](=[O:18])[C:7]1=[O:17])[CH3:16]
Reactant: CCn1c(=O)c(=O)[nH]c2cc(N)c([N+](=O)[O-])cc21
Agent: O=[Cu-]
Agent: O=N[O-]
Agent: O=S(=O)(O)O
Solvent: CCO
Solvent: CC(=O)O
Product: CCn1c(=O)c(=O)[nH]c2ccc([N+](=O)[O-])cc21
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 63.4 %

Procedure:
14.2 g (57 mmol) of 6-amino-1-ethyl-7-nitro-2,3(1H,4H)-quinoxalinedione (Example 30 a) were suspended in 340 ml of acetic acid. To this was added dropwise at 10°-20° C. a solution of 5.1 g (74 mmol) of sodium nitrite and 80 ml of concentrated sulfuric acid. The mixture was stirred for a further 30 minutes and then this solution was added dropwise to another suspension of 16.3 g (114 mmol) of copper(I) oxide in 140 ml ethanol. The mixture was stirred for a further 10 minutes and then poured into 1 l of ice-water. After filtration, the filtrate was extracted with methylene chloride and the organic phase was dried and concentrated under reduced pressure to yield 8.5 g (64%) of the product.
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[S:3][C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([N+]([O-])=O)[CH3:12])[CH:7]=[CH:8][CH:9]=1.Cl.[OH-:19].[Na+]>[Fe]>[F:1][C:2]([F:17])([F:16])[S:3][C:4]1[CH:5]=[C:6]([CH2:10][C:11](=[O:19])[CH3:12])[CH:7]=[CH:8][CH:9]=1
Reactant: [OH-]
Reactant: CC(=Cc1cccc(SC(F)(F)F)c1)[N+](=O)[O-]
Agent: [Fe]
Agent: Cl
Agent: [Na+]
Product: CC(=O)Cc1cccc(SC(F)(F)F)c1
Reaction time: 7 h
Yield: 60.5 %

Procedure:
13.2 g (50 mmols) of 1-(3'-trifluoromethylthio-phenyl)-2-nitro-propene, 19.6 g (0.35g atom) of iron powder and 0.25 g of ferric chloride are introduced into a 250 ml three-necked flask equipped with a mechanical stirrer, a condenser and a dropping funnel and this mixture is heated on an oil bath at 80°-90° C. 13.5 ml of concentrated hydrochloric acid are added dropwise, via the dropping funnel, with stirring, over the course of 7 hours, while the temperature is kept at 90° C. The reaction mixture is allowed to cool and rendered alkaline with sodium hydroxide solution. The ketone is then steam distilled. The distillate is extracted twice in succession with 100 ml. of diethyl ether each time. The two ether extracts are combined, dried over sodium sulphate and filtered. The solvent is evaporated from the filtrate in vacuo on a water bath, and the residue is rectified. 7.1g (60.5 % yield) of 1-(3'-trifluoromethylthio-phenyl)-2-propanone are thus obtained as a colourless oil, b.p. 138°-146° C/25-30 mm.Hg, nD23° = 1.489.
Reaction SMILES: [CH2:1]([C:4]1[S:5][C:6]([CH2:9][OH:10])=[CH:7][N:8]=1)[CH2:2][CH3:3]>[O-2].[O-2].[Mn+4].C1C=CC=CC=1>[CH2:1]([C:4]1[S:5][C:6]([CH:9]=[O:10])=[CH:7][N:8]=1)[CH2:2][CH3:3]
Reactant: CCCc1ncc(CO)s1
Agent: [Mn+4]
Agent: [O-2]
Solvent: c1ccccc1
Product: CCCc1ncc(C=O)s1
Temperature: 25 °C
Reaction time: 3 h
Yield: 89.2 %

Procedure:
A mixture of 21 g of 2-propyl-5-hydroxymethyl-thiazole, 1000 ml of benzene and 100 g of manganese dioxide was stirred at room temperature for 3 hours and after the addition of another 40 g of manganese dioxide, the mixture was stirred for 2 hours at room temperature. Another 20 g of manganese dioxide were added to the reaction mixture which was then stirred for 16 hours at room temperature and was filtered. The filter was washed with methylene chloride and the filtrate was evaporated to dryness under reduced pressure to obtain 18.5 g of 2-propyl-5-thiazolecarboxaldehyde.
Reaction SMILES: [CH2:1]1[CH:11]2[CH:12]3[CH:7]([CH2:8][CH2:9][CH2:10]2)[CH2:6][CH2:5][CH2:4][CH:3]3C1.[CH2:13]1C2=C3C(=CC=C2)C=CC=C3C1.CC12CC3CC(CC(C)(C3)C1)C2>>[CH2:4]([C:5]12[CH2:6][CH:7]3[CH2:8][CH:9]([CH2:10][CH:11]([CH2:12]3)[CH2:1]1)[CH2:13]2)[CH3:3]
Reactant: C1CC2CCCC3CCC(C1)C23
Reactant: c1cc2c3c(cccc3c1)CC2
Agent: CC12CC3CC(C1)CC(C)(C3)C2
Product: CCC12CC3CC(CC(C3)C1)C2

Procedure:
The same experiment as described in 2th line from the bottom in Table 5 of Example 5 was carried out except that perhydroacenaphthene prepared by hydrogenation of acenaphthene was used in place of TMN. Conversion rate of perhydroacenaphthene was 75.4%, and 1,3-dimethyladamantane and 1-ethyladamantane were obtained at 33.0% and 47.1% of selectivity and at 24.9% and 35.0% of yield respectively. Moreover, when amounts of catalyst was increased from 2 g to 4 g, conversion rate of perhydroacenaphthene was 85.6%, and 1,3-dimethyladamantane and 1-ethyladamantane were obtained at 45.2% and 6.6% of selectivity and at 38.7% and 5.7% of yield respectively.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][NH:15][CH2:16][CH:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:6]=1.[C:31]([C:35]1[CH:36]=[C:37]([CH:40]=[C:41]([C:43]([CH3:46])([CH3:45])[CH3:44])[CH:42]=1)[CH2:38]Br)([CH3:34])([CH3:33])[CH3:32].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:12][CH2:13][CH2:14][N:15]([CH2:16][CH:17]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:38][C:37]2[CH:36]=[C:35]([C:31]([CH3:33])([CH3:32])[CH3:34])[CH:42]=[C:41]([C:43]([CH3:46])([CH3:45])[CH3:44])[CH:40]=2)[CH:6]=1
Reactant: COC(=O)Cc1cccc(OCCCNCC(c2ccccc2)c2ccccc2)c1
Reactant: CC(C)(C)c1cc(CBr)cc(C(C)(C)C)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)Cc1cccc(OCCCN(Cc2cc(C(C)(C)C)cc(C(C)(C)C)c2)CC(c2ccccc2)c2ccccc2)c1
Temperature: 45 °C
Reaction time: 18 h
Yield: 92.4 %

Procedure:
To a solution of {3-[3-(2,2-diphenyl-ethylamino)-propoxy]-phenyl}-acetic acid methyl ester (3) (0.40 g, 0.001 mol) in DMF (10 mL), was added 3,5-di-tert-butyl-benzyl bromide (0.30 g, 0.0011 mol) and powdered potassium carbonate (0.96 g, 0.007 mol), the reaction mixture was heated and stirred at 45° C. for 18 hours. After cooling, the reaction mixture was diluted with water (30 mL) and extracted with EtOAc (3×25 mL). The combined organic extracts were washed with brine (15 mL), dried over Na2SO4, concentrated to an oil, which was purified by flash chromatography (9:1 Hexanes/EtOAc) to give the desired product as oil 0.56 g in 92% yield. 1H NMR (CDCl3) δ 7.19 (m, 10H), 7.12 (t, 2H), 7.01 (d, 2H), 6.82 (d, 1H), 6.63 (s, 1H), 6.59 (d, 1H), 4.17 (t, 1H), 3.67 (s, 3H), 3.62 (s, 2H), 3.57 (t, 2H), 3.55 (s, 2H), 3.10 (d, 2H), 2.58 (t, 2H), 1.77 (t, 2H), 1.26 (s, 18H). 13C NMR (CDCl3) δ 173.3, 160.6, 151.8, 145.1, 140.1, 136.5, 130.8, 129.8, 129.7, 129.6, 129.5, 127.6, 124.5, 122.6, 122.1, 117.0, 114.6, 67.3, 61.3, 53.4, 52.3, 51.2, 51.1, 42.7, 36.1, 32.9, 28.2.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.C[O:9][B:10](OC)[O:11]C.C([Li])(C)(C)C>C(OCC)C.CCCCC>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([B:10]([OH:11])[OH:9])[CH:3]=1
Reactant: COB(OC)OC
Reactant: Brc1cccnc1
Agent: [Li]C(C)(C)C
Solvent: CCOCC
Solvent: CCCCC
Product: OB(O)c1cccnc1
Temperature: 25 °C

Procedure:
A solution of 4.0 ml (6.56 g, 42 mmol) of 3-bromopyridine and 9 ml (8 mmol) of trimethylborate in 100 ml of diethyl ether was cooled to -70° C. then treated slowly with 33 ml (83.8 mmol) of a 2.54M tert-butyllithium in pentane solution. After allowing the resulting slurry to warm to room temperature the solvents were evaporated under vacuum. The residual oil was treated carefully with 50 ml of a 1M hydrochloric acid solution. Several milliters of methylene chloride were added and the mixture was stirred until the oil had dissolved. The aqueous layer was washed with fresh methylene chloride. The pH of the aqueous solution was raised to 12 with 5M sodium hydroxide solution and the washing was repeated. The pH of the aqueous solution was then lowered to 6.5 with concentrated hydrochloric acid solution. After chilling, this solution was filtered, saturated with sodium chloride, then extracted several times with a 2:1 mixture of diethyl ether and isopropanol. Evaporation of these extracts produced a colorless solid. This material was further purified by dissolving in methanol, evaporating to a thick paste, adding a few milliters of water, concentrating further under vacuum, then chilling and collecting the crystalline product. Additional product in the aqueous mother liquor was isolated by repeating this process. Thorough drying of this hydrated product at 0.1 mm pressure afforded a fine powder weighing 2.2 g. Elemental analysis and a mass spectrum indicated the product so isolated was primarily the anhydride (tripyridylboroxane).
Reaction SMILES: [CH2:1]1[C:10]2[C:5](=[CH:6][C:7]([N:11]3[CH2:15][C@H:14]([CH2:16][NH:17][C:18](=[O:20])[CH3:19])[O:13][C:12]3=[O:21])=[CH:8][CH:9]=2)[CH2:4][CH2:3][NH:2]1.CCN=C=NCCCN(C)C.Cl.[CH:34](O)=[O:35]>C1COCC1.O>[CH:34]([N:2]1[CH2:3][CH2:4][C:5]2[C:10](=[CH:9][CH:8]=[C:7]([N:11]3[CH2:15][C@H:14]([CH2:16][NH:17][C:18](=[O:20])[CH3:19])[O:13][C:12]3=[O:21])[CH:6]=2)[CH2:1]1)=[O:35]
Reactant: O=CO
Reactant: CC(=O)NC[C@H]1CN(c2ccc3c(c2)CCNC3)C(=O)O1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: O
Solvent: C1CCOC1
Product: CC(=O)NC[C@H]1CN(c2ccc3c(c2)CCN(C=O)C3)C(=O)O1
Temperature: 25 °C
Reaction time: 1.25 h
Yield: 73.4 %

Procedure:
A solution of N-[[(5S)-3-[1,2,3,4-tetrahydro-6-isoquinolinyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (Example 1, Step 6, 200 mg, 0.691 mmol) in THF is treated with EDC.HCl (172 mg, 0.899 mmol) and formic acid (34 μL, 0.899 mmol) to give a white slurry which is then diluted with H2O (approx. 2 mL) to give a homogeneous mixture. The mixture is stirred at ambient temperature for 1.25 hrs and is then diluted with H2O (10 mL) and extracted with CH2Cl2 (4×20 mL). The combined organic phase is washed with brine (10 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure, and the crude product is chromatographed on a Flash 40S silica gel (40 g, 32-63 μm) cartridge, eluting with a gradient of MeOH/CH2Cl2 (1/99-5/95). Those fractions with an Rf=0.41 by TLC (MeOH/CHCl3, 10/90) are pooled and concentrated and the resulting glassy solid is triturated with Et2O and filtered to give 161 mg (74%) of the title compound as a white solid, mp 139-141° C. (dec.). [α]25D=−22° (c 0.92, DMSO).