Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Li]CCCC.Br[C:7](Br)=[CH:8][CH:9]1[CH2:14][CH2:13][CH:12]([CH:15]2[CH2:20][CH2:19][CH:18]([C:21]3[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][CH3:29])=[CH:23][CH:22]=3)[CH2:17][CH2:16]2)[CH2:11][CH2:10]1.O.Cl>C1COCC1>[C:8]([CH:9]1[CH2:10][CH2:11][CH:12]([CH:15]2[CH2:20][CH2:19][CH:18]([C:21]3[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][CH3:29])=[CH:23][CH:22]=3)[CH2:17][CH2:16]2)[CH2:13][CH2:14]1)#[CH:7]
Reactant: CCCc1ccc(C2CCC(C3CCC(C=C(Br)Br)CC3)CC2)cc1
Agent: Cl
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Product: C#CC1CCC(C2CCC(c3ccc(CCC)cc3)CC2)CC1
Temperature: -20 °C
Reaction time: 2 h

Procedure:
23.7 ml (38.0 mmol) of n-BuLi are added to 7.70 g (16.4 mmol) of 4-(2,2-dibromovinyl)-4′-(4-propylphenyl)bicyclohexyl in 40 ml of THF at −75° C. When the addition is complete, the mixture is stirred at this temperature for 2 h and subsequently warmed to −20° C. Water and dil. hydrochloric acid are added, and the batch is extracted a number of times with MTBE. The combined organic phases are washed with water and sat. sodium chloride solution and dried using sodium sulfate. The solution is concentrated to completion, and the residue is purified by column chromatography (SiO2, n-heptane:1-chlorobutane=95:5). 4-Ethynyl-4′-(4-propylphenyl)bicyclohexyl is obtained as a colourless solid.
Reaction SMILES: [C:1]([N:5]1[C:10](=[O:11])[C:9](Cl)=[C:8]([Cl:13])[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2].Cl.[C:15]1(C)C=CC=CC=1>>[C:1]([N:5]1[C:10](=[O:11])[C:9]([CH3:15])=[C:8]([Cl:13])[CH:7]=[N:6]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1ccccc1
Reactant: CC(C)(C)n1ncc(Cl)c(Cl)c1=O
Agent: Cl
Product: Cc1c(Cl)cnn(C(C)(C)C)c1=O
Temperature: 0 °C

Procedure:
The resulting Grignard reagent was cooled to room temperature and was added dropwise over 20 minutes with 22.1 g (0.1 mol) of 2-tert.-butyl-4,5-dichloro-3(2H)-pyridazinone dissolved in 200 ml of dry toluene. After completion of adding, the reaction liquid was subjected to reaction for 1.5 hours at room temperature and then poured into a solution of 100 ml of conc. hydrochloric acid in 900 ml of ice-water to effect extraction. The resulting organic layer was then washed with 500 ml of 10% aqueous solution of sodium hydroxide and then with 500 ml of water, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to give 17.2 g of a crude product. The crude product was subjected to distillation (boiling point: 60° to 62° C./0.22 mmHg) and then column chromatography (silica gel; hexane:acetone=15:1) for separation and purification to give 4.5 g of 2-tert.-butyl-5-chloro-4-methyl-3(2H)-pyridazinone.
Reaction SMILES: [H-].[Na+].[CH2:3]([CH:5]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:4].[C:16]1([CH2:22][CH2:23][CH2:24][CH2:25][O:26][C:27]2[CH:32]=[CH:31][C:30]([CH2:33][CH2:34]I)=[CH:29][CH:28]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.O>CN(C)C=O>[CH2:3]([C:5]([CH2:34][CH2:33][C:30]1[CH:31]=[CH:32][C:27]([O:26][CH2:25][CH2:24][CH2:23][CH2:22][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:28][CH:29]=1)([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:4]
Reactant: ICCc1ccc(OCCCCc2ccccc2)cc1
Reactant: CCOC(=O)C(CC)C(=O)OCC
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)C(CC)(CCc1ccc(OCCCCc2ccccc2)cc1)C(=O)OCC
Temperature: 25 °C
Reaction time: 8 h
Yield: 99.3 %

Procedure:
To a suspension of sodium hydride (4.3 g) in dimethylformamide (212 ml) was added diethyl ethylmalonate (20 g) at 0° C. and the mixture was stirred at room temperature for an hour. To the solution, 2-(4-(4-phenylbutyloxy)phenyl)ethyl iodide (40 g) was dropwise added at 0° C., and the mixture was stirred for 20 minutes and allowed to stand at room temperature overnight. The reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed with water and a saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled away under reduced pressure and the residue obtained was purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=9:1) to give the subject compound (46 g).
Reaction SMILES: [CH:1]([C:4]1[NH:5][CH:6]=[CH:7][N:8]=1)([CH3:3])[CH3:2].[H-].[Na+].Cl[C:12]1[N:13]=[C:14]([N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)[C:15]2[S:20][C:19]([CH2:21][N:22]3[CH2:27][CH2:26][N:25](S(C)(=O)=O)[CH2:24][CH2:23]3)=[CH:18][C:16]=2[N:17]=1>CN(C)C=O.C(OCC)(=O)C>[CH:1]([C:4]1[N:5]([C:12]2[N:13]=[C:14]([N:32]3[CH2:33][CH2:34][O:35][CH2:36][CH2:37]3)[C:15]3[S:20][C:19]([CH2:21][N:22]4[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]4)=[CH:18][C:16]=3[N:17]=2)[CH:6]=[CH:7][N:8]=1)([CH3:3])[CH3:2]
Reactant: CS(=O)(=O)N1CCN(Cc2cc3nc(Cl)nc(N4CCOCC4)c3s2)CC1
Reactant: CC(C)c1ncc[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC(C)c1nccn1-c1nc(N2CCOCC2)c2sc(CN3CCNCC3)cc2n1
Temperature: 120 °C
Reaction time: 0.5 h

Procedure:
To 2-isopropylimidazole (28 mg) in dry N,N-dimethylformamide (1 ml) was added sodium hydride (10 mg, 60% dispersion in mineral oil). After 30 minutes, 2-chloro-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine, prepared via General Procedure B-3, was added and the reaction mixture was heated in the microwave for 45 minutes at 120° C. The reaction mixture was diluted with ethyl acetate, washed with water, dried (MgSO4) and the solvent removed in vacuo and the residue purified using flash chromatography to yield 176. NMR (400 MHz CDCl3): 1.19 (1H, s, CH), 1.30 (6H, d (J=6.84), 2.61-2.63 (4H, m, CH2), 2.74 (3H, s, CH3), 3.23-3.25 (4H, m, CH2), 3.79-3.82 (6H, m, CH2), 3.92-3.94 (4H, m, CH2), 6.92 (1H, s, ar), 7.18 (1H, s, ar), 7.66 (1H, d (J=1.49), ar). MH+506.30
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[CH:4]([CH:18]=O)[N:5]([CH:16]=O)[CH:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9][CH2:8][CH2:7]1.C([O-])(=O)C.[NH4+:25].C(O)(=O)C>O>[CH3:1][O:2][C:3]([C:4]1[N:5]([CH:6]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH2:9][CH2:8][CH2:7]2)[CH:16]=[N:25][CH:18]=1)=[O:20]
Reactant: COC(=O)C(C=O)N(C=O)C1CCCc2ccccc21
Reactant: [NH4+]
Agent: CC(=O)[O-]
Solvent: CC(=O)O
Solvent: O
Product: COC(=O)c1cncn1C1CCCc2ccccc21
Reaction time: 4 h

Procedure:
A mixture of 16.5 g of N,α-bis-formyl-N-(1,2,3,4-tetrahydronaphthalen-1-yl) glycine methyl ester, 65.0 g of ammonium acetate and 100 ml of acetic acid are refluxed for 8 hours. Then additional 50 g ammonium acetate are added and the refluxing is continued for further 4 hours. The solution is diluted with 300 ml of water and extracted twice, with 100 ml of toluene each time. The organic phases are combined, concentrated and separated at silica gel by chromatography. Concentration of the eluate yields 1-(1,2,3,4-tetrahydronaphthalen-1-yl) -5-imidazolecarboxylic acid methyl ester, having a melting point of 63° C.
Reaction SMILES: [F:1][C:2]([F:52])([F:51])[C:3]1[CH:4]=[C:5]([C:13]([CH3:50])([CH3:49])[C:14]([N:16]([CH3:48])[C:17]2[C:18]([C:40]3[CH:45]=[CH:44][C:43]([F:46])=[CH:42][C:41]=3[CH3:47])=[CH:19][C:20]([C@@H:23]3[N:27](C(OC(C)(C)C)=O)[C@:26]([CH3:39])([C:35]([O:37][CH3:38])=[O:36])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(O)(C(F)(F)F)=O>ClCCl>[F:52][C:2]([F:1])([F:51])[C:3]1[CH:4]=[C:5]([C:13]([CH3:49])([CH3:50])[C:14]([N:16]([CH3:48])[C:17]2[C:18]([C:40]3[CH:45]=[CH:44][C:43]([F:46])=[CH:42][C:41]=3[CH3:47])=[CH:19][C:20]([C@@H:23]3[NH:27][C@:26]([CH3:39])([C:35]([O:37][CH3:38])=[O:36])[CH2:25][CH2:24]3)=[N:21][CH:22]=2)=[O:15])[CH:6]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:8]=1
Reactant: COC(=O)[C@]1(C)CC[C@H](c2cc(-c3ccc(F)cc3C)c(N(C)C(=O)C(C)(C)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)cn2)N1C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COC(=O)[C@]1(C)CC[C@H](c2cc(-c3ccc(F)cc3C)c(N(C)C(=O)C(C)(C)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)cn2)N1
Temperature: 25 °C
Reaction time: 2 h
Yield: 97.1 %

Procedure:
To a solution of 1-(1,1-dimethylethyl) 2-methyl (2S,5R)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-methyl-1,2-pyrrolidinedicarboxylate (Intermediate 8, 50 mg, 0.068 mmol) in dry Dichloromethane (3 ml) was added TFA (1 ml, 12.98 mmol) and the reaction mixture was stirred for 2 hours at r.t. The solvent and the excess of TFA were evaporated and the residue was purified by SPE-SCX cartridge affording the title compound (42 mg, 0.066 mmol, 97% yield) as a white solid. HPLC: Rt 5.79 min. MS: m/z 640 [M+H]+ and 662 [M+Na]+.
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][C:6]2([CH3:14])[CH3:13].C1(S)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>CN1C(=O)CCC1>[OH:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][C:6]2([CH3:14])[CH3:13]
Reactant: COc1ccc2c(c1)C(C)(C)CC2=O
Agent: O=C([O-])[O-]
Agent: Sc1ccccc1
Agent: [K+]
Solvent: CN1CCCC1=O
Product: CC1(C)CC(=O)c2ccc(O)cc21
Temperature: 220 °C

Procedure:
In a microwave reaction tube, a mixture of 5-methoxy-3,3-dimethyl-indan-1-one (880 mg, 4.63 mmol), benzenethiol (510 mg, 4.63 mmol), and potassium carbonate (64 mg, 0.46 mmol) in NMP (5 mL) is purged with N2. The reaction mixture is heated at 220° C. for 30 min under microwave irradiation. The reaction mixture made to alkaline with 1N aqueous NaOH (10 mL) and extracted with Et2O (3×20 mL). The aqueous part is acidified in an ice bath with 6N HCl and extracted with Et2O (3×20 mL). The combined organic phases are washed with brine and dried over Na2SO4. After concentration, the crude product is purified with silica gel column chromatography (30% ethyl acetate in hexanes) to afford 5-hydroxy-3,3-dimethyl-indan-1-one as a yellow solid: 1H NMR (400 MHz, CDCl3) δ 7.63 (d, 1H, J=8 Hz), 6.88 (d, 1H, J=2 Hz), 6.84 (dd, 1H, J=2, 8 Hz), 6.14 (s, 1H), 2.59 (s, 2H), 1.40 (s, 6H), ESMS m/z 177.1 (M+H+).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:7]=[C:8]([N+:10]([O-:12])=[O:11])[CH:9]=1)[NH2:6].[CH3:13][S:14](Cl)(=[O:16])=[O:15]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:6][S:14]([CH3:13])(=[O:16])=[O:15])[CH:7]=[C:8]([N+:10]([O-:12])=[O:11])[CH:9]=1
Reactant: COc1cc(N)cc([N+](=O)[O-])c1
Reactant: CS(=O)(=O)Cl
Product: COc1cc(NS(C)(=O)=O)cc([N+](=O)[O-])c1
Yield: 102.5 %

Procedure:
3-Methoxy-5-nitroaniline (2 g, 11.89 mmol) was treated with methanesulfonyl chloride (1.01 ml, 13.08 mmol) according to the method described in Preparation 15b to give 3 g (100% yield) of the title compound. Purity 97%.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[Li]C(C)(C)C.[CH2:16]([N:23]1[CH2:28][CH2:27][C:26](=[O:29])[CH2:25][CH2:24]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[NH4+].[Cl-]>CCOCC>[CH2:16]([N:23]1[CH2:28][CH2:27][C:26]([OH:29])([CH2:2][CH2:3][CH2:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH2:25][CH2:24]1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: BrCCCc1ccccc1
Reactant: O=C1CCN(Cc2ccccc2)CC1
Agent: [Cl-]
Agent: [Li]C(C)(C)C
Agent: [NH4+]
Solvent: CCOCC
Product: OC1(CCCc2ccccc2)CCN(Cc2ccccc2)CC1
Temperature: -20 °C
Reaction time: 0.25 h
Yield: 77.3 %

Procedure:
To a solution of 3.8 mL (25 mmol) of 1-bromo-3-phenyl propane in 200 mL of ether at −78° C. was slowly added 30 mL (50 mmol) of t-BuLi (1.7 M in pentane). The reaction mixture was warmed to −20° C. for 15 min, then it was recooled to −78° C. To this reaction mixture was slowly added a solution of 2.61 g (13.8 mmol) of 1-benzyl-4-piperidone in 20 mL of ether. After 15 min, the reaction mixture was poured into, 200 mL of sat'd NH4Cl solution. The reaction mixture was extracted with ethyl acetate and the combined organic fractions were washed with sat'd NaCl solution, dried over MgSO4 filtered and the filtrate was concentrated. The residue was purified by chromatography (silica, hexanes: ethyl acetate, 1:1) to give 3.3 g of the title compound.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)(=O)[CH3:2].Cl.[N+:11]([C:14]1[CH:22]=[CH:21][C:17]([CH2:18][O:19][NH2:20])=[CH:16][CH:15]=1)([O-:13])=[O:12]>>[N+:11]([C:14]1[CH:15]=[CH:16][C:17]([CH2:18][O:19]/[N:20]=[C:1](/[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)\[CH3:2])=[CH:21][CH:22]=1)([O-:13])=[O:12]
Reactant: CC(=O)c1ccccc1
Reactant: NOCc1ccc([N+](=O)[O-])cc1
Agent: Cl
Product: C/C(=N\OCc1ccc([N+](=O)[O-])cc1)c1ccccc1
Yield: 76.4 %

Procedure:
Acetophenone (20) (150 mg, 1.25 mmol) was condensed with compound 19 (280 mg, 1.37 mmol) according to the general procedure II-A defined above. After heating the reaction mixture for 2 h it was cooled and the solvent removed under reduced pressure. The resulting solid was filtered off and washed with cold isopropanol (3.0 mL) to afford the title compound CP30252 (258 mg, 77%) as a pale-yellow solid, m.p. 91.3-92.3° C.
Reaction SMILES: [Na].[NH2:2][C:3]1[N:8]=[C:7]([NH2:9])[C:6](I)=[C:5]([CH3:11])[N:4]=1.[CH3:12][C:13]([C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=1)([CH3:19])/[CH:14]=[CH:15]/B(O)O>C(O)C>[NH2:2][C:3]1[N:8]=[C:7]([NH2:9])[C:6](/[CH:15]=[CH:14]/[C:13]([C:20]2[CH:21]=[CH:22][C:23]([C:26]([F:27])([F:29])[F:28])=[CH:24][CH:25]=2)([CH3:12])[CH3:19])=[C:5]([CH3:11])[N:4]=1
Reactant: CC(C)(/C=C/B(O)O)c1ccc(C(F)(F)F)cc1
Reactant: Cc1nc(N)nc(N)c1I
Agent: [Na]
Solvent: CCO
Product: Cc1nc(N)nc(N)c1/C=C/C(C)(C)c1ccc(C(F)(F)F)cc1
Temperature: 80 °C
Reaction time: 28 h
Yield: 56.5 %

Procedure:
Sodium metal, 4.1 grams (0.18 mole), was stirred with 250 mL of ethanol for 30 minutes. After this time 20.0 grams (0.08 mole) of 2,4-diamino-5-iodo-6-methylpyrimidine (prepared in Step B of Example 3), 27.6 grams (0.11 mole) of trans-3-methyl-3-(4-trifluoromethylphenyl)-1-butenylboronic acid, and 9.2 grams (0.008 mole) of tetrakistriphenylphosphine palladium(0) were added. The reaction mixture was purged with nitrogen, and then heated to 80° C. where it stirred for about 28 hours. After this time the reaction mixture was concentrated under reduced pressure to about 20% of the original volume and then poured into 300 mL of water. The mixture was cooled in an ice-bath, and a solid was collected by filtration. The solid was triturated with a mixture of 1:1 petroleum ether:diethyl ether, and then subjected to column chromatography on silica gel using 5% methanol in methylene chloride as the eluant. The product-containing fractions were combined and concentrated under reduced pressure to a solid residue. The solid was recrystallized from 1-propanol and water, yielding 15.2 grams of trans-2,4-diamino-6-methyl-5-[3-(4-trifluoromethylphenyl)-3-methyl-1-butenyl]pyrimidine, mp 182°-185° C. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6](Cl)[CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[CH3:12][C:13]1[CH:18]=[CH:17][C:16]([SH:19])=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[NH2:1][C:2]1[CH:7]=[C:6]([S:19][C:16]2[CH:17]=[CH:18][C:13]([CH3:12])=[CH:14][CH:15]=2)[CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10]
Reactant: Nc1cc(Cl)ccc1[N+](=O)[O-]
Reactant: Cc1ccc(S)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc(Sc2ccc([N+](=O)[O-])c(N)c2)cc1

Procedure:
A mixture of 2.5 g. 2-amino-4-chloro-1-nitrobenzene, 3.6 g. p-thiocresol, 4.2 g. potassium carbonate in 20 ml. dimethylformamide is stirred overnight at room temperature, then poured into water. The crude product, recrystallized from methanol, gives 2-amino-4-(p-methylphenylthio)-1-nitrobenzene.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[N:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][C:12]([N+:18]([O-])=O)=[CH:13][CH:14]=2)[C:9]1=[O:21]>CO.C(Cl)(Cl)Cl.[Pd]>[NH2:18][C:12]1[CH:11]=[C:10]2[C:15]([CH:16]=[CH:17][N:8]([C:3]3[CH:4]=[N:5][CH:6]=[CH:7][C:2]=3[CH3:1])[C:9]2=[O:21])=[CH:14][CH:13]=1
Reactant: Cc1ccncc1-n1ccc2ccc([N+](=O)[O-])cc2c1=O
Agent: [Pd]
Solvent: ClC(Cl)Cl
Solvent: CO
Product: Cc1ccncc1-n1ccc2ccc(N)cc2c1=O
Reaction time: 3.3 h
Yield: 79.9 %

Procedure:
10% Pd—C (20 mg) was added to a solution of 2-(4-methyl-pyridin-3-yl)-7-nitro-2H-isoquinolin-1-one (I-24b: 140 mg, 0.4982 mmol) in methanol (8 mL) under nitrogen atmosphere. The resulting mixture was hydrogenated in a Parr hydrogenator at room temperature for 3.30 hours. The reaction was monitored by TLC (5% methanol in CHCl3). The reaction mixture was filtered; the filtrate was concentrated and dried to afford 100 mg of the product (79.9% yield).
Reaction SMILES: FC(F)(F)C(O)=O.[OH:8][C:9]1[CH:36]=[CH:35][C:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[CH:33][C:10]=1[C:11]([NH:13][C:14]1[CH:26]=[C:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:24]=[CH:23][C:15]=1[C:16]([O:18]C(C)(C)C)=[O:17])=[O:12]>C(Cl)Cl>[OH:8][C:9]1[CH:36]=[CH:35][C:34]([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)=[CH:33][C:10]=1[C:11]([NH:13][C:14]1[CH:26]=[C:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:24]=[CH:23][C:15]=1[C:16]([OH:18])=[O:17])=[O:12]
Reactant: CC(C)(C)OC(=O)c1ccc(-c2ccccc2)cc1NC(=O)c1cc(-c2ccccc2)ccc1O
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(Nc1cc(-c2ccccc2)ccc1C(=O)O)c1cc(-c2ccccc2)ccc1O
Temperature: 25 °C
Reaction time: 17 h
Yield: 96.3 %

Procedure:
Trifluoroacetic acid (1 mL) was added to a methylene chloride (3 mL) solution of the obtained tert-butyl 2-(2-hydroxy-5-phenylbenzamido)-4-phenylbenzoate (0.085 g), followed by stirring at room temperature for 17 hours. The solvent was evaporated under reduced pressure, and ethyl acetate was added to the residue. The solid substance was collected by filtration to obtain 0.072 g of 2-(2-hydroxy-5-phenylbenzamido)-4-phenylbenzoic acid as a white solid.
Reaction SMILES: [CH3:1][C:2]1[NH:7][C:6](=[O:8])[C:5]([CH:9]=O)=[CH:4][CH:3]=1.CCN(CC)CC.[CH3:18][C:19](OC(C)=O)=[O:20]>>[CH3:1][C:2]1[N:7]=[C:6]2[O:8][C:19](=[O:20])[CH:18]=[CH:9][C:5]2=[CH:4][CH:3]=1
Reactant: CC(=O)OC(C)=O
Reactant: Cc1ccc(C=O)c(=O)[nH]1
Solvent: CCN(CC)CC
Product: Cc1ccc2ccc(=O)oc2n1
Temperature: 120 °C
Yield: 30 %

Procedure:
To 6-methyl-2-oxo-1,2-dihydro-3-pyridinecarbaldehyde (318 mg, 2.3 mmol) in Ac2O (3 mL) was added Et3N (1 mL). The reaction was heated at 120° C. for 18 hours. The reaction was concentrated and the resulting material was dissolved in MeOH and loaded onto silica gel and evaporated. Purification by column chromatography (silica gel) using a hexanes/ethyl acetate gradient (0-100% EtOAc) provided the desired product as a solid (80 mg, 30%). LCMS (ES+) m/z 162 (MH+).
Reaction SMILES: [C:1](O)(=O)[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][CH2:15][CH2:16][CH2:17][CH3:18].C(Cl)([Cl:23])=O>>[CH2:1]([Cl:23])[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][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: O=C(Cl)Cl
Reactant: CCCCCCCCCCCCCCCCCC(=O)O
Product: CCCCCCCCCCCCCCCCCCCl
Yield: 99.9 %

Procedure:
The experimental method described in Example 1 is used, and 2,746 g (10 moles) of technical grade stearic acid and the catalyst phase (342 g) obtained in Example 1 are initially taken. 1,089 g (11 moles) of gaseous phosgene are then introduced. The product phase contains 2,930 g (99.9% yield) of stearyl chloride having a purity of 97% (determined by IR spectroscopy); the iodine color number is 30.
Reaction SMILES: [OH2:1].[C:2]([C:24](F)=[O:25])([C:5]([C:8]([C:11]([C:14]([C:17]([C:20]([F:23])([F:22])[F:21])([F:19])[F:18])([F:16])[F:15])([F:13])[F:12])([F:10])[F:9])([F:7])[F:6])([F:4])[F:3].F>>[C:2]([C:24]([OH:25])=[O:1])([C:5]([C:8]([C:11]([C:14]([C:17]([C:20]([F:22])([F:21])[F:23])([F:19])[F:18])([F:15])[F:16])([F:12])[F:13])([F:10])[F:9])([F:6])[F:7])([F:3])[F:4]
Reactant: O=C(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Reactant: O
Agent: F
Product: O=C(O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F

Procedure:
A 500 ml PFA vessel equipped with a stirrer was used. Water (250 g, 13.9 mol) was temperature conditioned to 15° C. within the vessel, following which C7F15COF (125 g, 0.3 mol) having a purity of 99.9 wt % was added dropwise under stirring. The resulting mixture was a solid-liquid dispersed system composed of an aqueous phase containing the hydrogen fluoride that formed in hydrolysis, and a solid phase of the C7F15COOH that formed in hydrolysis.
Reaction SMILES: [CH3:1][C:2]1[C:6](B(O)O)=[C:5]([CH3:10])[O:4][N:3]=1.Br[C:12]1[CH:13]=[C:14]([CH:16]=[CH:17][CH:18]=1)[NH2:15].C([O-])([O-])=O.[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][C:2]1[C:6]([C:12]2[CH:13]=[C:14]([NH2:15])[CH:16]=[CH:17][CH:18]=2)=[C:5]([CH3:10])[O:4][N:3]=1
Reactant: Nc1cccc(Br)c1
Reactant: Cc1noc(C)c1B(O)O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: Cc1noc(C)c1-c1cccc(N)c1
Temperature: 25 °C
Yield: 71 %

Procedure:
3,5-dimethylisoxazole-4-boronic acid (0.123 g, 0.872 mmol) and 3-bromoaniline (0.063 mL, 0.581 mmol) were combined in DME (2 mL) in a flame-dried, round-bottom flask. Na2CO3 (2M, 0.610 mL, 1.22 mmol) and Pd(PPh3)4 (0.02 g, 0.017 mmol) were added to the stirred solution. The reaction was refluxed overnight under argon flow, and subsequently cooled to room temperature. The solvent was removed under vacuum and the resulting residue was resuspended in CH2Cl2. The organic phase was dried over MgSO4, filtered, and concentrated under vacuum. The crude product was purified by flash silica column chromatography (10-60% EtOAc/hexanes). The purification was monitored by TLC. The solvent was removed under vacuum from fractions containing product, resulting in 0.077 g in 71% yield.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[CH2:6][CH2:5]2.[BH4-].[Na+]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7]([OH:11])[CH2:6][CH2:5]2
Reactant: O=C1CCc2cc(Br)ccc21
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Product: OC1CCc2cc(Br)ccc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 98.8 %

Procedure:
To a solution of 5-bromo-1-indanone (2.0 g, 9.5 mmol) in THF (20 mL) was added NaBH4 (0.5 g, 12.8 mmol). After stirring at room temperature overnight, the solution was quenched by addition of water. The resulting solution was extracted with EtOAc twice. The combined EtOAc layers were dried over Na2SO4 and concentrated under vacuum to give 2.0 g of the title compound as a solid. MS calculated for C9H9BrO: (M+H)+ 212.9. found 194.9 (M+H-H2O)+ , 197.0 (M+H-H2O)+.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:30])[C@@H:13]([NH:19][C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:21])[CH2:14][CH:15]([OH:18])[CH2:16][OH:17])[CH2:8][CH2:7]1)=[O:5])[CH3:2].[C:31]1(C)[CH:36]=CC(S(O)(=O)=O)=C[CH:32]=1.COC(OC)(C)C>ClCCl>[CH2:1]([O:3][C:4]([N:6]1[CH2:7][CH2:8][N:9]([C:12](=[O:30])[C@@H:13]([NH:19][C:20]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:21])[CH2:14][CH:15]2[CH2:16][O:17][C:31]([CH3:36])([CH3:32])[O:18]2)[CH2:10][CH2:11]1)=[O:5])[CH3:2]
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: CCOC(=O)N1CCN(C(=O)[C@H](CC(O)CO)NC(=O)OCc2ccccc2)CC1
Solvent: ClCCl
Solvent: COC(C)(C)OC
Product: CCOC(=O)N1CCN(C(=O)[C@H](CC2COC(C)(C)O2)NC(=O)OCc2ccccc2)CC1
Reaction time: 1 h

Procedure:
To a solution of 755 mg 4-((S)-2-Benzyloxycarbonylamino-4,5-dihydroxy-pentanoyl)-piperazine-1-carboxylic acid ethyl ester in 10 ml dichloromethane were added 10 mg p-toluenesulfonic acid and 10 ml 2,2-dimethoxypropane and the solution stirred for 1 h. The reaction mixture was concentrated, the residue dissolved in dichloromethane and washed with saturated aqueous NaHCO3 and brine. The crude product obtained after evaporation of the solvent was directly used in the next reaction step. Yield: 612 mg.