Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C@H:2]1[O:10][C@@H:9]([CH3:11])[C@@H:7]([OH:8])[C@@H:5]([OH:6])[C@@H:3]1[OH:4].[C:18](Cl)(=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20]>N1C=CC=CC=1.CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:18]([O:4][C@H:3]1[C@H:5]([O:6][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C@H:7]([O:8][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[C@H:9]([CH3:11])[O:10][C@@H:2]1[S:1][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)(=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20]
Reactant: CC(C)(C)C(=O)Cl
Reactant: C[C@@H]1O[C@H](Sc2ccccc2)[C@@H](O)[C@H](O)[C@@H]1O
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: C[C@@H]1O[C@H](Sc2ccccc2)[C@@H](OC(=O)C(C)(C)C)[C@H](OC(=O)C(C)(C)C)[C@@H]1OC(=O)C(C)(C)C
Temperature: 100 °C

Procedure:
To a solution of crude phenyl 6-deoxy-1-thio-β-L-galactopyranoside 3 in 15 mL of pyridine is added pivaloyl chloride (4.0 mL, 3.90 g, 32.5 mmol) and DMAP (0.33 g, 2.71 mmol). The reaction mixture is heated at 100° C. for 12 h, cooled, diluted with 50 mL of CH2Cl2, washed with H2O (100 mL) and saturated NaCl (100 mL), dried over Na2SO4, filtered and concentrated to afford 3.25 g of phenyl 6-deoxy-2,3,4-tri-O-pivaloyl-1-thio-β-L-galactopyranoside 4 as a brown oil. This oil is purified by flash chromatography (15% EtOAc/petroleum ether) to afford 0.53 g (48%) of the pure compound. An additional 0.81 g of a brown oil, which that appeared to be a mixture of incompletely acylated products, is also isolated. This material is resubjected to the reaction conditions for 48 h and provided an additional 0.21 g (19%, total yield 67% for 2 steps): Rf 0.48 (15% EtOAc/petroleum ether); 1H NMR (CDCl3, 270 MHz) δ 7.50-7.59 (m, 2H), 7.23-7.35 (m, 3H), 5.16-5.30 (m, 2H), 5.08 (dd, J=9.9, 3.0 Hz, 1H, H-3), 4.66 (d, J=9.6 Hz, 1H, H-1), 3.90 (q, J=6.3 Hz, 1H, H-5), 1.21 (s, 9H), 1.18 (s, 9H), 1.21 (s, 9H), 1.21 (d, J=6.6 Hz, 3H, H-6); 13C NMR (CDCl3, 68 MHz) δ 177.2, 177.4, 177.1, 133.5, 131.1, 128.6, 128.4, 128.1, 127.7, 85.1, 73.3, 72.6, 69.9, 66.3, 38.9, 38.6, 26.9, 27.0, 16.4; FABMS C27H39O7S (MNa+) calcd 531.2392, found 531.2404.
Reaction SMILES: [CH2:1](Cl)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C([Mg:22][Cl:23])CCCCCCC>>[CH2:1]([Mg:22][Cl:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCC[Mg]Cl
Reactant: CCCCCCCCCCCCCl
Product: CCCCCCCCCCCC[Mg]Cl
Yield: 92.5 %

Procedure:
The compound n-C12H25MgCl was prepared from Mg and n-C12H25Cl by operating according to the modalities described in Example 1(a) for the compound n-C8H17MgCl.
Reaction SMILES: [OH2:1].[OH-].[Na+].Cl[C:5]1([CH2:8][C:9]([CH2:11][C:12]2([Cl:15])[CH2:14][CH2:13]2)=O)[CH2:7][CH2:6]1.[Cl:16][C:17]1C=CC(C=O)=[CH:19][CH:18]=1>C(O)C>[Cl:16][C:17]1[CH:6]=[CH:7][C:5]([CH:8]=[CH:9][C:11]([C:12]2([Cl:15])[CH2:13][CH2:14]2)=[O:1])=[CH:19][CH:18]=1
Reactant: O
Reactant: O=Cc1ccc(Cl)cc1
Reactant: O=C(CC1(Cl)CC1)CC1(Cl)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(C=Cc1ccc(Cl)cc1)C1(Cl)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 89 %

Procedure:
50 ml of water and 10 pellets of solid sodium hydroxide are added at room temperature to a mixture of 60 g (0.5 mol) of 1-chlorocyclopropylmethyl ketone, 70 g (0.5 mol) of 4-chlorobenzaldehyde and 250 ml of ethanol. The mixture is stirred at room temperature for 16 hours. The precipitated solid is then filtered off with suction. In this manner, 108.5 g (89% of theory) of 1-chlorocyclopropyl 4-chlorophenyl-ethenyl ketone are obtained in the form of a solid substance of melting point 92° C.
Reaction SMILES: S(Cl)([Cl:3])=O.[N+:5]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][C:15]([OH:17])=O)([O-:7])=[O:6]>C1C=CC=CC=1>[N+:5]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH2:14][C:15]([Cl:3])=[O:17])([O-:7])=[O:6]
Reactant: O=C(O)Cc1ccccc1[N+](=O)[O-]
Reactant: O=S(Cl)Cl
Solvent: c1ccccc1
Product: O=C(Cl)Cc1ccccc1[N+](=O)[O-]

Procedure:
Thionylchloride (12.0 g) and 18.11 g of 2-nitrophenylacetic acid are weighed into a flask and allowed to stand at room temperature (~21°) for 16 hours. A stirring bar is added and the reaction driven to completion by warming at 35° for five additional hours until no solid is visible. To the red solution is added 5 ml benzene and the volatile material is removed with vacuum to give 2-nitrophenyacetyl chloride.
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][C:8]([NH2:10])=[CH:9][C:4]=2[N:3]=[CH:2]1.[N:11]1[O:15][N:14]=[C:13]2[CH:16]=[C:17]([CH:20]=O)[CH:18]=[CH:19][C:12]=12.C([O:24][C:25](=O)[C:26](=[O:31])[CH2:27][C:28](=[O:30])[CH3:29])C>C(O)C>[C:28]([C:27]1[CH:20]([C:17]2[CH:18]=[CH:19][C:12]3=[N:11][O:15][N:14]=[C:13]3[CH:16]=2)[N:10]([C:8]2[CH:7]=[CH:6][C:5]3[NH:1][CH:2]=[N:3][C:4]=3[CH:9]=2)[C:25](=[O:24])[C:26]=1[OH:31])(=[O:30])[CH3:29]
Reactant: O=Cc1ccc2nonc2c1
Reactant: CCOC(=O)C(=O)CC(C)=O
Reactant: Nc1ccc2[nH]cnc2c1
Solvent: CCO
Product: CC(=O)C1=C(O)C(=O)N(c2ccc3[nH]cnc3c2)C1c1ccc2nonc2c1
Temperature: 50 °C
Reaction time: 24 h

Procedure:
1H-Benzoimidazol-5-ylamine (1 mmol) and Benzo[1,2,5]oxadiazole-5-carbaldehyde (1 mmol) were added to ethanol (5 ml). After 30 min 2,4-Dioxo-pentanoic acid ethyl ester (1 mmol) was added. The reaction was heated to 50° C. and stirred for 24 h. After evaporation of the solvent the residue was purified with chromatographic methods.
Reaction SMILES: [F:1][C:2]([F:22])([F:21])[C:3]1[C:4]([N:9]2[CH2:15][CH2:14][C:13]3[C:16](O)=[N:17][CH:18]=[N:19][C:12]=3[CH2:11][CH2:10]2)=[N:5][CH:6]=[CH:7][CH:8]=1.O=P(Cl)(Cl)Cl.CCO[C:31]([CH3:33])=O>CC#N>[C:3]([C:31]1[CH:33]=[CH:13][C:12]([NH:19][C:16]2[C:13]3[CH2:14][CH2:15][N:9]([C:4]4[C:3]([C:2]([F:22])([F:21])[F:1])=[CH:8][CH:7]=[CH:6][N:5]=4)[CH2:10][CH2:11][C:12]=3[N:19]=[CH:18][N:17]=2)=[CH:11][CH:10]=1)([CH3:4])([CH3:8])[CH3:2]
Reactant: Oc1ncnc2c1CCN(c1ncccc1C(F)(F)F)CC2
Reactant: CCOC(C)=O
Solvent: CC#N
Solvent: O=P(Cl)(Cl)Cl
Product: CC(C)(C)c1ccc(Nc2ncnc3c2CCN(c2ncccc2C(F)(F)F)CC3)cc1
Temperature: 90 °C
Yield: 33 %

Procedure:
To a solution of 7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepin-4-ol (185 mg, 0.60 mmol) in CH3CN (2 mL) was added POCl3 (0.11 mL, 1.19 mmol). The reaction mixture was heated at 90° C. for 2 h. The mixture was cooled to rt, diluted with EtOAc, and quenched slowly with saturated (satd.) aq. NaHCO3. The combined organic layers were dried (Na2SO4) and concentrated. The crude residue was purified (FCC) to give the title compound (65 mg, 33%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:11]=[C:10]([N:12]2[CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[CH2:14][CH2:13]2)[S:9][N:8]=1.Cl.CCCCCC>O1CCCC1.C(OCC)(=O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]1[N:11]=[C:10]([N:12]2[CH2:13][CH2:14][NH:15][CH2:16][CH2:17]2)[S:9][N:8]=1
Reactant: CC(C)(C)OC(=O)N1CCN(c2nc(-c3ccccn3)ns2)CC1
Agent: Cl
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: c1ccc(-c2nsc(N3CCNCC3)n2)nc1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
tert-Butyl 4-(3-pyridin-2-yl-1,2,4-thiadiazol-5-yl)piperazine-1-carboxylate (6.35 g, 17.0 mmol) was dissolved in tetrahydrofuran (100 ml), and a solution of 4 N hydrogen chloride in ethyl acetate (50 ml) was added thereto, followed by stirring at room temperature for 5 hours. Hexane (250 ml) was poured to the reaction mixture, and a solid was separated by filtration. The obtained solid was dissolved in an aqueous saturated sodium hydrogen carbonate solution, followed by stirring at room temperature for 2 hours. Water was poured to the reaction mixture, and the resulting solution was extracted with a mixed solution of ethyl acetate/tetrahydrofuran (1:1). The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. Hexane was added to the residue, and 2.79 g (67.0%) of the desired product as a solid was separated by filtration.
Reaction SMILES: [Br:1][C:2]1[C:11]([CH2:12]Br)=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([O:14][CH3:15])=[N:9]2)=[CH:4][CH:3]=1.C([O-])(O)=[O:17].[Na+]>CC(C)=O.O>[Br:1][C:2]1[C:11]([CH2:12][OH:17])=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([O:14][CH3:15])=[N:9]2)=[CH:4][CH:3]=1
Reactant: O=C([O-])O
Reactant: COc1ccc2ccc(Br)c(CBr)c2n1
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: COc1ccc2ccc(Br)c(CO)c2n1
Yield: 56 %

Procedure:
A suspension of 7-bromo-8-bromomethyl-2-methoxyquinoline (35.2 g; prepared according to WO 2007/081597) and NaHCO3 (14.63 g) in acetone (430 mL) and water (430 mL) was refluxed for 6 h. The org. solvent was removed under reduced pressure and the aq. layer was extracted twice with EA. The combined org. layers were sequentially washed with water and brine and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was crystallized from TBDME, affording an off-white solid (16.01 g; 56% yield).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[CH2:26](Br)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.O>CN(C=O)C>[CH2:26]([O:11][C:10](=[O:12])[C@H:9]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:9][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:15][CH:14]=1)[NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1
Reactant: CC(C)(C)OC(=O)N[C@H](C(=O)O)c1ccc(O)cc1
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)OC(=O)N[C@H](C(=O)OCc1ccccc1)c1ccc(OCc2ccccc2)cc1
Temperature: 50 °C
Reaction time: 17 h
Yield: 184 %

Procedure:
To a solution of (S)-tert-butoxycarbonylamino-(4-hydroxy-phenyl)-acetic acid (32.03 g, 120 mmol) in DMF (300 ml) was added potassium carbonate (35 g, 252 mmol) and benzylbromide (30 ml, 252 mmol). The reaction mixture was stirred at 50° C. under a nitrogen atmosphere for 17 h. The mixture was poured into water (1l) and extracted with EtOAc (3×600 ml). The combined organic extracts were washed with water (3×600 ml), brine (600 ml), dried over magnesium sulfate, filtered and evaporated in vacuo to yield a yellow oil (49.4 g, 92%). LCMS purity 100%, m/z 470 [M++Na]+.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[CH:11][C:12]1[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=1)[C:6]([CH3:24])=[C:5]2[CH2:25][C:26](NCC(O)=O)=[O:27].C([O:40]C(=O)CNC(=O)CC1C2C(=CC=C(F)C=2)C(=CC2C=C(OC)C(OC)=C(OC)C=2)C=1C)C1C=CC=CC=1>C(O)C.[OH-].[Na+].O>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[CH:11][C:12]1[CH:13]=[C:14]([O:22][CH3:23])[C:15]([O:20][CH3:21])=[C:16]([O:18][CH3:19])[CH:17]=1)[C:6]([CH3:24])=[C:5]2[CH2:25][C:26]([OH:40])=[O:27]
Reactant: COc1cc(C=C2C(C)=C(CC(=O)NCC(=O)O)c3cc(F)ccc32)cc(OC)c1OC
Reactant: COc1cc(C=C2C(C)=C(CC(=O)NCC(=O)OCc3ccccc3)c3cc(F)ccc32)cc(OC)c1OC
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: COc1cc(C=C2C(C)=C(CC(=O)O)c3cc(F)ccc32)cc(OC)c1OC
Reaction time: 18 h

Procedure:
N-[5-fluoro-2-methyl-1-(3,4,5-trimethoxybenzylidene)-3-indenylacetyl]-glycine. Benzyl-N-[5-fluoro-2-methyl-1-(3,4,5-trimethoxy-benzylidene)-3-indenylacetyl]-glycinate (0.03 mol) in a mixture of 25 ml of anhydrous ethanol and 2.5 ml of 1 N sodium hydroxide is allowed to stand at room temperature for 18 h. The solution is diluted with water and extracted with ether. The aqueous layer is acidified with dilute hydrochloric acid and the organic product is extracted with ethyl acetate, washed with water and dried over sodium sulfate. Evaporation of the solution gives N-[5-fluoro-2-methyl-1-(3,4,5-trimethoxybenzylidene)-3-indenylacetic acid, the corresponding indenyl acyl glycine is obtained.
Reaction SMILES: [C:1]([C:4]1[C:9]([OH:10])=[C:8]([CH3:11])[C:7]([CH3:12])=[C:6]([OH:13])[C:5]=1[CH3:14])(=[O:3])[CH3:2].[CH3:15][O:16][CH:17]([O:21][CH3:22])[C:18](=O)[CH3:19].N1CCCC1>C1(C)C=CC=CC=1>[CH3:15][O:16][CH:17]([O:21][CH3:22])[C:18]1([CH3:19])[CH2:2][C:1](=[O:3])[C:4]2[C:9](=[C:8]([CH3:11])[C:7]([CH3:12])=[C:6]([OH:13])[C:5]=2[CH3:14])[O:10]1
Reactant: COC(OC)C(C)=O
Reactant: CC(=O)c1c(C)c(O)c(C)c(C)c1O
Solvent: Cc1ccccc1
Solvent: C1CCNC1
Product: COC(OC)C1(C)CC(=O)c2c(C)c(O)c(C)c(C)c2O1
Yield: 70 %

Procedure:
15.0 g (77 mmoles) of acetyl-trimethylhydroquinone, 10.5 g (89 mmoles) of 1,1-dimethoxy-propan-2-one and 9.30 g (131 mmoles) of pyrrolidine were reacted in toluene solution by a method similar to that of Example 1 to give the above product. Boiling point: 165°-170° C./6.10-5 mbar (bulb tube); yield: 70%.
Reaction SMILES: [OH-:1].[Na+].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]2[C:17](=[C:18]3[CH2:23][CH2:22][N:21](OCC)[C:20](=[C:27]=[O:28])[CH2:19]3)[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[CH2:10][CH2:9][C:8]=2[CH:29]=1>C(O)C>[C:27]([OH:28])(=[O:1])[CH3:20].[Cl:3][C:4]1[CH:5]=[CH:6][C:7]2[C:17](=[C:18]3[CH2:19][CH2:20][NH:21][CH2:22][CH2:23]3)[C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[CH2:10][CH2:9][C:8]=2[CH:29]=1
Reactant: [OH-]
Reactant: CCON1CCC(=C2c3ccc(Cl)cc3CCc3cccnc32)CC1=C=O
Agent: [Na+]
Solvent: CCO
Product: CC(=O)O
Product: Clc1ccc2c(c1)CCc1cccnc1C2=C1CCNCC1
Reaction time: 24 h

Procedure:
To 12 grams of sodium hydroxide in 30 mL ethyl alcohol (70%) add 6 grams of 8-chloro-6,11-dihydro-11-(1-ethoxy-carbonyl-4-piperidylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (prepared as described in U.S. Pat. No. 4,282,233) and reflux with stirring for 24 hours. After about the first 6-8 hours an additional 30 mL of 70% ethyl alcohol may be added.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][CH2:14][C:15]1[N:16]=[N:17][NH:18][N:19]=1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH2:53]([O:57][C:58]([N:60]1[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]1)=[O:59])[CH2:54][CH2:55][CH3:56]>CN(C=O)C.C(Cl)Cl>[CH2:53]([O:57][C:58]([N:60]1[CH2:65][CH2:64][N:63]([C:10](=[O:12])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:14][C:15]2[N:16]=[N:17][NH:18][N:19]=2)[CH2:62][CH2:61]1)=[O:59])[CH2:54][CH2:55][CH3:56]
Reactant: CC(C)(C)OC(=O)N[C@@H](CCc1nn[nH]n1)C(=O)O
Reactant: CCCCOC(=O)N1CCNCC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CCCCOC(=O)N1CCN(C(=O)[C@H](CCc2nn[nH]n2)NC(=O)OC(C)(C)C)CC1

Procedure:
To a solution of 500 mg (S)-2-tert-butoxycarbonylamino-4-(2H-tetrazol-5-yl)-butyric acid in 20 ml DMF were added 701 mg HATU, 457 μl DIPEA and 343 mg 1-butoxycarbonyl-piperazine. After 3 h the solution was concentrated, the residue obtained diluted with DCM and subsequently washed with aqueous LiCl (4%) and 0.1 M HCl. The organic layer was dried over MgSO4 and concentrated. Yield: 730 mg.
Reaction SMILES: [CH3:1][NH:2][C:3]1[O:8][C:7](=[O:9])[C:6]2[C:10]([CH3:14])=[CH:11][CH:12]=[CH:13][C:5]=2[N:4]=1.C(OC(=O)C)(=[O:17])C.N1[CH:27]=[CH:26]C=CC=1.CN(C1C=CC=CN=1)C>O1CCCC1>[CH3:26][CH2:27][C:1]([NH:2][C:3]1[O:8][C:7](=[O:9])[C:6]2[C:10]([CH3:14])=[CH:11][CH:12]=[CH:13][C:5]=2[N:4]=1)=[O:17]
Reactant: CNc1nc2cccc(C)c2c(=O)o1
Reactant: c1ccncc1
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccccn1
Solvent: C1CCOC1
Product: CCC(=O)Nc1nc2cccc(C)c2c(=O)o1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a solution of 200 mg 2-methylamino-5-methyl-4H-3,1-benzoxazin-4-one, prepared as described in Example I, above, in 20 ml of dry tetrahydrofuran, was added 3 ml of acetic anhydride, 3 ml of pyridine and 25 mg of dimethylaminopyridine. The solution was stirred at room temperature for 3 days. The solvent was removed under reduced pressure, and remaining trace amounts of acetic anhydride and pyridine were removed by azeotroping with toluene. The residue was purified by column chromatography over silica gel (10% ethyl acetate:petroleum ether, 30°-60° C.) to yield 210 mg of 2-(N-methylacetylamino)-5-methyl-4H-3,1-benzoxazin-4-one, m.p. 108°-109° C., 'H NMR: (delta CDCl3); 2.6 (s, 3H, CH3 -Ar), 2.8 (s, 3H, CH3), 3.4 (s, 3H, NMe), 7.1-7.8 (m, 3H, Ar-H); IR: 1765, 1690, 1640, 1620, 1600 cm-1.
Reaction SMILES: [PH3]=[O:2].[OH:3][C:4]([CH3:22])([CH3:21])[CH2:5][CH2:6][P:7](=[O:20])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[C:23]1(C)C=[CH:27][C:26](S(O)(=O)=O)=[CH:25][CH:24]=1>C1C=CC=CC=1>[O:2]1[CH2:27][CH2:26][CH2:25][CH2:24][CH:23]1[O:3][C:4]([CH3:22])([CH3:21])[CH2:5][CH2:6][P:7](=[O:20])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: O=[PH3]
Reactant: CC(C)(O)CCP(=O)(c1ccccc1)c1ccccc1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Product: CC(C)(CCP(=O)(c1ccccc1)c1ccccc1)OC1CCCCO1
Reaction time: 20 h

Procedure:
The phosphine oxide from (f) above (1.4 g) was dissolved in dihydripyran (20 ml) and benzene (5 ml). p-Toluenesulphonic acid (10 mg) was added. After 20 hr, the mixture was concentrated, added to CH2Cl2 and washed with 5% aqueous NaHCO3 /brine and dried. Evaporation of the solvent gave the crude product (1.8 g) essentially quantitatively as a solid. Recrystallised from acetone. m.p. 146°-148° C.; 1Hnmr δ 8.0-7.3 (m, 10 H, aryl), 4.67 (m, W=6 Hz, THP, C-2'H), 3.67 (m, W=36 Hz, THP, C-6'H2), 1.23 (s, 6H); IR νmax 2950 (m), 1440 (m), 118C (s), cm-1 ; (analysis found: % C, 70.80; H, 7.73; P, 8.54; C22H29O3P requires % C, 70.96; H, 7.85; P, 8.32.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][N:5]=[CH:4][C:3]=1[CH3:11].[CH3:12][NH2:13].[CH3:14][C@H:15]1[CH2:20][CH2:19][CH2:18][N:17]([CH2:21][CH2:22][CH2:23][O:24][C:25]2[CH:32]=[CH:31][C:28]([CH:29]=O)=[CH:27][CH:26]=2)[CH2:16]1>>[CH3:12][N:13]1[C:8](=[O:10])[C:7]2[CH:6]=[N:5][CH:4]=[C:3]([CH3:11])[C:2]=2[N:1]=[C:29]1[C:28]1[CH:31]=[CH:32][C:25]([O:24][CH2:23][CH2:22][CH2:21][N:17]2[CH2:18][CH2:19][CH2:20][C@H:15]([CH3:14])[CH2:16]2)=[CH:26][CH:27]=1
Reactant: CN
Reactant: Cc1cncc(C(=O)O)c1N
Reactant: C[C@H]1CCCN(CCCOc2ccc(C=O)cc2)C1
Product: Cc1cncc2c(=O)n(C)c(-c3ccc(OCCCN4CCC[C@H](C)C4)cc3)nc12

Procedure:
The entitled compound was obtained according to the method of Example 15 but starting from 4-amino-5-methylnicotinic acid, methylamine and 4-{3-[(3S)-3-methylpiperidin-1-yl]propoxy}benzaldehyde.
Reaction SMILES: Cl[P:2]([CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)[CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.Cl.C1(C)C=CC=CC=1>CN(C)C=O.[Zn]>[CH:9]1([PH:2][CH:3]2[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]2)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]1
Reactant: ClP(C1CCCCC1)C1CCCCC1
Agent: Cl
Agent: [Zn]
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: C1CCC(PC2CCCCC2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 67 %

Procedure:
1.09 g (4.68 mmol) of chlorodicyclohexylphosphine was added dropwise in a nitrogen gas atmosphere to a suspension of 461 mg (7.05 mg-atoms) of zinc (powder) in 10 cm3 of N,N-dimethylformamide and the mixture was stirred at room temperature for one hour. To the reaction mixture was added dropwise 10 cm3 (10 mmol) of 1 mol·dm--3 hydrochloric acid and then 10 cm3 of toluene. The mixture was stirred, the aqueous layer and the toluene layer were separated off, and the toluene layer was determined by gas chromatography, giving dicyclohexylphosphine in 67% yield.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N+:4]([O-])[CH:5]=[C:6]([Cl:8])[CH:7]=1.C[Si]([C:14]#[N:15])(C)C.C(N(CC)CC)C>C(#N)C>[C:14]([C:3]1[C:2]([Cl:1])=[CH:7][C:6]([Cl:8])=[CH:5][N:4]=1)#[N:15]
Reactant: [O-][n+]1cc(Cl)cc(Cl)c1
Reactant: C[Si](C)(C)C#N
Solvent: CCN(CC)CC
Solvent: CC#N
Product: N#Cc1ncc(Cl)cc1Cl
Yield: 94.8 %

Procedure:
3,5-Dichloropyridine-N-oxide (10.0 g, 61 mmol), trimethysilylcyanide (25 mL, 183 mmol) and triethylamine (17 mL, 122 mmol) combined in acetonitrile (60 mL) and heated to reflux for 6 hr. The solvent was evaporated and the residue was partitioned between diethyl ether and 5% aq. NaHCO3. The organic phase was dried (MgSO4), evaporated, and the product purified by chromatography over silica gel to yield 10.0 g (97%) of the title compound: 1H NMR (300 MHz, CDCl3) δ 7.92 (d, 1H), 8.58 (d, 1H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:18]=[CH:17][C:16]([S:19]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=3)(=[O:21])=[O:20])=[CH:15][C:14]=2[CH2:29][OH:30])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].CC([N-]C(C)C)C.[CH3:39][N:40]([CH3:44])[C:41](Cl)=[O:42]>C1COCC1.O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([C:13]2[CH:18]=[CH:17][C:16]([S:19]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=3)(=[O:21])=[O:20])=[CH:15][C:14]=2[CH2:29][O:30][C:41](=[O:42])[N:40]([CH3:44])[CH3:39])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(S(=O)(=O)c3cccc(F)c3)cc2CO)C1
Reactant: CN(C)C(=O)Cl
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: CN(C)C(=O)OCc1cc(S(=O)(=O)c2cccc(F)c2)ccc1C1CCN(C(=O)OC(C)(C)C)C1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 96.4 %

Procedure:
3-[4-(3-Fluoro-benzenesulfonyl)-2-hydroxymethyl-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (74 mg, 0.170 mmol) was dissolved in 25 ml of THF and the mixture was cooled to −78° C. LDA (0.102 ml, 0.204 mmol) was added and allowed to stir for 30 minutes. Dimethylcarbamoyl chloride (0.023 ml, 0.255 mmol) was added and the mixture was allowed to warm to room temperature over 3 hours. The mixture was diluted with water and extracted with EtOAc. The combined organic extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (CH2Cl2/MeOH 95/5) to give 83 mgs (96%) of 3-[2-Dimethylcarbamoyloxymethyl-4-(3-fluoro-benzenesulfonyl)-phenyl]-pyrrolidine-1-carboxylic acid tert-butyl ester as a clear oil.
Reaction SMILES: [OH:1]N1[C:6](=O)[C:5]2=[CH:8][CH:9]=[CH:10][CH:11]=[C:4]2[C:3]1=[O:12].[O-]O.[C:15]1(C(C)C)[CH:20]=CC=[CH:17][CH:16]=1.[CH2:24]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1>>[CH:3]1([OH:12])[CH2:4][CH2:11][CH2:10][CH2:9][CH2:8][CH2:5][CH2:6][CH2:17][CH2:16][CH2:15][CH2:20]1.[C:24]1(=[O:1])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.[CH2:24]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1
Reactant: CC(C)c1ccccc1
Reactant: O=C1c2ccccc2C(=O)N1O
Agent: C1CCCCCCCCCCC1
Agent: [O-]O
Product: O=C1CCCCCCCCCCC1
Product: OC1CCCCCCCCCCC1
Reaction time: 8 h

Procedure:
2 mmol of N-hydroxyphthalimide and 4 mmol of cumene hydroperoxide are added at a temperature of 130° C. to 200 mmol of cyclododecane in a round-bottomed flask having an attached reflux condenser. Air at approximately 15 l/h is passed through the reaction mixture for 8 hours at said temperature. Cyclododecanol is obtained at a selectivity of 18% and cyclododecanone at a selectivity of 42%, at a cyclododecane conversion rate of 47%.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:23])[CH2:5][S:6]([C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)=[CH:11][CH:10]=1)(=[O:8])=[O:7])[CH3:2].[CH2:24]([N:28]([CH2:32][CH2:33]Cl)[CH2:29][CH2:30]Cl)[CH2:25][CH2:26][CH3:27]>>[CH2:1]([O:3][C:4]([C:5]1([S:6]([C:9]2[CH:10]=[CH:11][C:12]([O:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:33][CH2:32][N:28]([CH2:24][CH2:25][CH2:26][CH3:27])[CH2:29][CH2:30]1)=[O:23])[CH3:2]
Reactant: CCOC(=O)CS(=O)(=O)c1ccc(Oc2ccc(Cl)cc2)cc1
Reactant: CCCCN(CCCl)CCCl
Product: CCCCN1CCC(C(=O)OCC)(S(=O)(=O)c2ccc(Oc3ccc(Cl)cc3)cc2)CC1

Procedure:
1-Butyl-4-[4-(4-chloro-phenoxy)-benzenesulfonyl]-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method outlined in example 83 starting from [4-(4-chloro-phenoxy)-benzenesulfonyl]-acetic acid ethyl ester (6 g, 18.3 mmol) and butyl-bis-(2-chloro-ethyl)-amine (5.2 g, 22 mmol). Yield 3.3 g (38%); yellow oil; MS: 480 (M+H)+