Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:5]1[CH:25]=[CH:24][C:8]2[NH:9][C:10]([C@@H:12]([NH:16]C(=O)OC(C)(C)C)[C@H:13]([OH:15])[CH3:14])=[N:11][C:7]=2[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:16][C@H:12]([C:10]1[NH:9][C:8]2[CH:24]=[CH:25][C:5]([C:1]([CH3:2])([CH3:4])[CH3:3])=[CH:6][C:7]=2[N:11]=1)[C@H:13]([OH:15])[CH3:14]
Reactant: C[C@@H](O)[C@H](NC(=O)OC(C)(C)C)c1nc2cc(C(C)(C)C)ccc2[nH]1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: C[C@@H](O)[C@H](N)c1nc2cc(C(C)(C)C)ccc2[nH]1
Temperature: 25 °C
Yield: 28.1 %

Procedure:
To tert-butyl [(1R,2R)-1-(5-tert-butyl-1H-benzimidazol-2-yl)-2-hydroxypropyl]-carbamate (105 mg, 0.302 mmol) was added DCM (5 mL) followed by TFA (700 μL) at 0° C. The reaction was allowed to warm to room temperature for 4 hours before cooling back to 0° C. and quenching with saturated aqueous NaHCO3 solution (20 mL). The mixture was extracted with DCM, the organic layer collected, dried over MgSO4 and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with DCM:MeOH:NH3 (80:20:2) to afford the title compound (21 mg, 28%).
Reaction SMILES: [C:1]1([NH:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:14](Cl)(=[O:18])[C:15](Cl)=[O:16].Cl>C1(C)C=CC=CC=1>[C:8]1([N:7]2[C:1]3[C:2](=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:15](=[O:16])[C:14]2=[O:18])[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: O=C(Cl)C(=O)Cl
Reactant: c1ccc(Nc2ccccc2)cc1
Agent: Cl
Solvent: Cc1ccccc1
Product: O=C1C(=O)N(c2ccccc2)c2ccccc21
Temperature: 60 °C
Yield: 94.2 %

Procedure:
The title compound is prepared following the procedures of Bryant, N. M., III et al. Syn Commun, 23, 1617-25 (1993) as follows. A solution of diphenylamine (26.6 g, 157 mmol) in toluene (65 mL) is added slowly to a solution of oxalyl chloride (14.8 mL, 170 mmol) in toluene (35 mL) while cooling in an ice-water bath to maintain the temperature below 40° C. The resulting brown slurry is heated at 55-65° C. for 1 hr. CAUTION: There is vigorous evolution of hydrogen chloride gas. Approximately 100 mL of solvent is removed by distillation (it contains unreacted oxalyl chloride) and the residue is heated overnight at 118-125° C. The reaction is cooled and then poured into ice-water (200 mL), extracted with ethyl acetate (4×250 mL). The combined extract is dried, filtered and concentrated to give 1-phenyl-1H-indole-2,3-dione (33.0 g, 94% yield). H-NMR 7.70 (1H, d), 7.58 (3H, d), 7.43 (3H, m), 7.19 (1H, t), 6.90 (1H, d).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)=[N:8][CH:9]=1)([O-])=O.[H][H]>C(O)C.O1CCCC1.[Pd]>[F:19][C:16]([F:17])([F:18])[C:13]1[CH:12]=[CH:11][C:10]([C:7]2[N:8]=[CH:9][C:4]([NH2:1])=[CH:5][CH:6]=2)=[CH:15][CH:14]=1
Reactant: O=[N+]([O-])c1ccc(-c2ccc(C(F)(F)F)cc2)nc1
Reactant: [H][H]
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCO
Product: Nc1ccc(-c2ccc(C(F)(F)F)cc2)nc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 95.2 %

Procedure:
To a solution of 5-nitro-2-(4-(trifluoromethyl)phenyl)pyridine (260 mg, 0.97 mmol) in ethanol (10 mL) and tetrahydrofuran (5 mL) was added 10 wt % palladium on carbon (100 mg). The reaction was pressurized to 50 psi hydrogen and stirred at room temperature for 4 hours. The reaction was filtered through Celite and concentrated to give 6-(4-(trifluoromethyl)phenyl)pyridin-3-amine (220 mg, 95%). 1H NMR (400 MHz, CD3OD, δ): 7.98 (s, 1H), 7.88 (d, 2H), 7.60 (d2, H), 7.54 (d, 1H), 7.09 (d, 1H).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].Cl.[C:8]([O:11][CH2:12][CH2:13][C@@H:14]([C:16]([OH:18])=[O:17])[NH2:15])(=[O:10])[CH3:9].C(OC(=O)C[C:24](=[O:29])[C:25]([F:28])([F:27])[F:26])C.Cl>C(O)C.O>[F:26][C:25]([F:28])([F:27])[C:24]([NH:15][C@H:14]([C:16]([OH:18])=[O:17])[CH2:13][CH2:12][O:11][C:8](=[O:10])[CH3:9])=[O:29]
Reactant: CCOC(=O)CC(=O)C(F)(F)F
Reactant: CC(=O)OCC[C@H](N)C(=O)O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCO
Product: CC(=O)OCC[C@H](NC(=O)C(F)(F)F)C(=O)O
Reaction time: 14 h
Yield: 45.1 %

Procedure:
7.6 g (55 mol) of potassium carbonate are added to a suspension of 9.9 g (50 mmol) of O-acetyl-L-homoserine hydrochloride and 7.8 g (55 mmol) of trifluoroacetylacetic acid ethyl ester in 200 ml of ethanol, and stirring is carried out for 14 hours. 10.8 g (110 mmol) of 37% hydrochloric acid and 200 ml of water are then added. The product obtained after removal of the ethanol by distillation is filtered off with suction, washed with water and dried. 5.8 g (45%) of N-trifluoroacetyl-O-acetyl-L-homo-serine are obtained.
Reaction SMILES: [CH3:1][C:2]1[CH:17]=[CH:16][C:15]([Si:18]([CH3:21])([CH3:20])[CH3:19])=[CH:14][C:3]=1[O:4][C:5]1[O:9][C:8]([C:10]([O:12]C)=[O:11])=[CH:7][CH:6]=1.[OH-].[Na+]>CO.O>[CH3:1][C:2]1[CH:17]=[CH:16][C:15]([Si:18]([CH3:19])([CH3:21])[CH3:20])=[CH:14][C:3]=1[O:4][C:5]1[O:9][C:8]([C:10]([OH:12])=[O:11])=[CH:7][CH:6]=1
Reactant: COC(=O)c1ccc(Oc2cc([Si](C)(C)C)ccc2C)o1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: Cc1ccc([Si](C)(C)C)cc1Oc1ccc(C(=O)O)o1
Reaction time: 18 h
Yield: 87.8 %

Procedure:
To a solution of methyl 5-[2-methyl-5-(trimethylsilyl)phenoxy]furan-2-carboxylate (Intermediate 4; 217 mg, 0.71 mmol) in methyl alcohol (3 mL) at room temperature was added a solution of sodium hydroxide (126 mg) in water (1 mL) and the reaction stirred for 18 hours. The resulting mixture was concentrated under reduced pressure, the residue taken up in water and extracted into diethyl ether (1×20 mL). The aqueous layer was acidified with hydrochloric acid (1 M) and extracted with ethyl acetate (2×25 mL). The organic extracts were dried (magnesium sulphate) and concentrated under reduced pressure to give the title compound as a colourless powder (181 mg, 87%). Rf=0.21 (9:1, dichloromethane-methyl alcohol). LCMS Rt=4.33 minutes, m/z=291 (MH+).
Reaction SMILES: Cl[C:2]1[N:7]=[N:6][C:5]([C:8]2[CH:49]=[CH:48][C:11]([CH2:12][C:13]3[N:14]([C:26]4[CH:27]=[C:28]([N:32]5[S:36](=[O:38])(=[O:37])[N:35]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])[C:34](=[O:47])[CH2:33]5)[CH:29]=[CH:30][CH:31]=4)[CH:15]=[C:16]([C:18]4[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=4[Cl:25])[N:17]=3)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[C:50]1(B(O)O)[CH2:55][CH2:54][CH2:53][CH2:52][CH:51]=1>>[C:50]1([C:2]2[N:7]=[N:6][C:5]([C:8]3[CH:9]=[CH:10][C:11]([CH2:12][C:13]4[N:14]([C:26]5[CH:27]=[C:28]([N:32]6[S:36](=[O:38])(=[O:37])[N:35]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:45])([CH3:46])[CH3:44])[C:34](=[O:47])[CH2:33]6)[CH:29]=[CH:30][CH:31]=5)[CH:15]=[C:16]([C:18]5[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=5[Cl:25])[N:17]=4)=[CH:48][CH:49]=3)=[CH:4][CH:3]=2)[CH2:55][CH2:54][CH2:53][CH2:52][CH:51]=1
Reactant: OB(O)C1=CCCCC1
Reactant: C[Si](C)(C)CCOCN1C(=O)CN(c2cccc(-n3cc(-c4ccc(Cl)cc4Cl)nc3Cc3ccc(-c4ccc(Cl)nn4)cc3)c2)S1(=O)=O
Product: C[Si](C)(C)CCOCN1C(=O)CN(c2cccc(-n3cc(-c4ccc(Cl)cc4Cl)nc3Cc3ccc(-c4ccc(C5=CCCCC5)nn4)cc3)c2)S1(=O)=O

Procedure:
5-{3-[2-[4-(6-Chloro-pyridazin-3-yl)-benzyl]-4-(2,4-dichloro-phenyl)-imidazol-1-yl]-phenyl}-1,1-dioxo-2-(2-trimethylsilanyl-ethoxymethyl)-[1,2,5]thiadiazolidin-3-one (76 mg, 0.1 mmol) was treated as described in general procedure G using 1-cyclohexen-1-yl-boronic acid (51 mg, 0.4 mmol) to give 5-{3-[2-[4-(6-cyclohex-1-enyl-pyridazin-3-yl)-benzyl]-4-(2,4-dichloro-phenyl)-imidazol-1-yl]-phenyl}-1,1-dioxo-2-(2-trimethylsilanyl-ethoxymethyl)-[1,2,5]thiadiazolidin-3-one, which was then dissolved in 1 mL dry acetic acid, iron powder (−325 mesh, 112 mg, 2 mmol) was added and the mixture was then heated at 100° C. under nitrogen for 2 days. At completion, the reaction mixture was then diluted with water/EtOAc and the leftover iron powder was filtered and washed with EtOAc. The combined organic layer was washed with water, saturated NaHCO3 and brine. The organic layer was then dried over Na2SO4, filtered, and the filtrate was concentrated and purified by silica gel chromatography to afford 5-{3-[2-[4-(6-cyclohexyl-pyridazin-3-yl)-benzyl]-4-(2,4-dichloro-phenyl)-imidazol-1-yl]-phenyl}-1,1-dioxo-2-(2-trimethylsilanyl-ethoxymethyl)-[1,2,5]thiadiazolidin-3-one.
Reaction SMILES: Cl.[CH:2]1([CH2:8][C@@H:9]([C:11]([OH:13])=[O:12])[NH2:10])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[CH2:14]([O:21][C:22](Cl)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>[OH-].[Na+].O1CCCC1>[CH2:14]([O:21][C:22]([NH:10][C@H:9]([C:11]([OH:13])=[O:12])[CH2:8][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: N[C@@H](CC1CCCCC1)C(=O)O
Reactant: O=C(Cl)OCc1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=C(N[C@@H](CC1CCCCC1)C(=O)O)OCc1ccccc1
Reaction time: 1.5 h
Yield: 68.9 %

Procedure:
To a solution of 3-cyclohexylalanine, hydrochloride (4.75 , 22.8 mmol) in 2N sodium hydroxide (11.4 mL) were added at 0° C., simultaneously, a solution of benzylchloroformate (3.2 mL, 36 mmol) in tetrahydrofuran (10 mL) and 2N sodium hydroxide (11.4 mL). (The pH of the mixture was maintained around 9-10 by addition of 2N sodium hydroxide.) The mixture was stirred for 1.5 hours. The solution was washed with diethyl ether (3×20 mL). The aqueous phase was acidified to pH 2 with 3N aqueous hydrochloric acid and extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over anhydrous magnesium sulphate. Filtration and removal of the solvent in vacuo left 4.80 g of the expected product (yellow oil, 69% yield).
Reaction SMILES: [Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([C:12]3[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=3)[C:15]#[N:16])[C:7](=[O:20])[C@@H:6]([CH2:21]O)[N:5]([CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[C:4]=2[N:3]=1.C(N(S(F)(F)[F:34])CC)C>C(Cl)Cl>[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([C:12]3[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=3)[C:15]#[N:16])[C:7](=[O:20])[C@@H:6]([CH2:21][F:34])[N:5]([CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[C:4]=2[N:3]=1
Reactant: CCN(CC)S(F)(F)F
Reactant: N#Cc1cccc(N2C(=O)[C@@H](CO)N(C3CCCC3)c3nc(Cl)ncc32)c1
Solvent: ClCCl
Product: N#Cc1cccc(N2C(=O)[C@@H](CF)N(C3CCCC3)c3nc(Cl)ncc32)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 25.9 %

Procedure:
To a stirred solution of 3-[(7R)-2-chloro-8-cyclopentyl-7-(hydroxymethyl)-6-oxo-7,8-dihydropteridin-5(6H)-yl]benzonitrile (94 mg, 0.24 mmol) in anhydrous DCM (3 mL) was added diethylaminosulfur trifluoride (39 μL, 0.29 mmol) at −78° C. under nitrogen. The mixture was allowed to warm to rt and stirred for 18 h. The mixture was then cooled to 0° C. and quenched by saturated aqueous NaHCO3 solution. The mixture was extracted with DCM (30 mL×2) and the combined organic layers were dried over Na2SO4, concentrated in vacuo to give a crude residue, which was purified using a silica gel flash chromatography [eluent: 0-50% EtOAc/Heptane] to afford the desired compound (24 mg, 25%). 1H NMR (400 MHz, CD3OD): δ 7.89-7.94 (m, 1H), 7.74-7.80 (m, 2H), 7.61-7.66 (m, 1H), 7.01 (s, 1H), 4.87-5.00 (m, 1H), 4.70-4.83 (m, 1H), 4.31 (quin, J=8.4 Hz, 1H), 2.08-2.19 (m, 2H), 1.97-2.07 (m, 4H), 1.61-1.76 (m, 2H). MS (ES+): m/z=386.32/388.29 [MH+]. UPLC: tR=1.33 min (TOF: polar_2 min).
Reaction SMILES: C[Mg]Br.[C:4]([C:6]1[CH:11]=[CH:10][C:9]([C:12]([F:15])([F:14])[F:13])=[CH:8][CH:7]=1)#[CH:5].CON(C)[C:19]([C:21]1[N:25]([CH3:26])[N:24]=[CH:23][CH:22]=1)=[O:20].[Cl-].[NH4+]>O1CCCC1>[CH3:26][N:25]1[C:21]([C:19](=[O:20])[C:5]#[C:4][C:6]2[CH:11]=[CH:10][C:9]([C:12]([F:13])([F:14])[F:15])=[CH:8][CH:7]=2)=[CH:22][CH:23]=[N:24]1
Reactant: C#Cc1ccc(C(F)(F)F)cc1
Reactant: CON(C)C(=O)c1ccnn1C
Agent: C[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: Cn1nccc1C(=O)C#Cc1ccc(C(F)(F)F)cc1
Temperature: -78 °C
Reaction time: 2 h

Procedure:
Methyl magnesium bromide (9.70 mL, 1.0 M tetrahydrofuran solution) was added dropwise to a tetrahydrofuran (4.0 mL) solution of 1-ethynyl-4-(trifluoromethyl)benzene (1.80 mL) under cooling in an ice bath, and the obtained solution was then stirred for 2 hours. Thereafter, the reaction solution was cooled to −78° C., and a tetrahydrofuran (6.2 mL) solution of N-methoxy-N,1-dimethyl-1H-pyrazol-5-carboxamide (867 mg) was then added thereto. The obtained mixture was stirred for 1 hour, and was then stirred for 2.5 hours under cooling in an ice bath. Thereafter, a saturated ammonium chloride aqueous solution was added to the reaction solution, and the obtained mixture was then extracted with ethyl acetate. The organic layer was washed with a saturated saline, and was then dried over anhydrous magnesium sulfate, followed by vacuum concentration. The residue was purified by column chromatography (silica gel cartridge, hexane:ethyl acetate=9:1), so as to obtain the title compound (1.09 g) in the form of a yellow oily substance.
Reaction SMILES: [NH2:1][C:2]1[C:3]([Br:20])=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=O)[C:6]([CH2:18][CH3:19])([CH2:12][CH2:13][C:14](=[O:17])[CH2:15][CH3:16])[CH2:5]2.C([O-])([O-])=O.[K+].[K+]>C(O)(=O)C.Cl.CCOC(C)=O>[NH2:1][C:2]1[C:3]([Br:20])=[C:4]2[C:8]([C:7]3[C:6]([CH2:18][CH3:19])([CH2:5]2)[CH2:12][CH2:13][C:14](=[O:17])[C:15]=3[CH3:16])=[CH:9][CH:10]=1
Reactant: CCC(=O)CCC1(CC)Cc2c(ccc(N)c2Br)C1=O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CCC12CCC(=O)C(C)=C1c1ccc(N)c(Br)c1C2
Temperature: 80 °C
Reaction time: 72 h
Yield: 90.3 %

Procedure:
The crude diketone (1.17 g) from step 3 was dissolved in acetic acid (14 mL) and the solution was diluted with aqueous 6N HCl (14 mL). The resulting mixture was stirred and heated in an oil bath at 80° C. for 5 hours and then kept at room temperature for 3 days. The mixture was diluted with EtOAc (100 mL) and carefully basified with aqueous K2CO3 (200 mL). The organic portion was washed with brine, dried over MgSO4 filtered, and evaporated under vacuum. The residue was lyophilized from benzene to afford crude 7-amino-8-bromo-9a-ethyl-4-methyl-1,2,9,9a-tetrahydro-3H-fluoren-3-one (1.0 g) as an amorphous solid.
Reaction SMILES: CO.C(OC([NH:13][CH2:14][CH2:15][CH2:16][CH2:17][C@H:18]([OH:23])[CH2:19][C:20]([NH2:22])=[O:21])=O)C1C=CC=CC=1>[C].[Pd].C(O)(=O)C>[NH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C@H:18]([OH:23])[CH2:19][C:20]([NH2:22])=[O:21]
Reactant: NC(=O)C[C@@H](O)CCCCNC(=O)OCc1ccccc1
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CO
Product: NCCCC[C@H](O)CC(N)=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 105.4 %

Procedure:
Into a mixture of 10 ml of 90% aqueous methanol and 0.01 ml of acetic acid, was dissolved 350 mg (1.19 mmoles) of (S)-7-benzyloxycarbonylamino-3-hydroxyheptanamide. After addition of 50 mg of 5% palladium-carbon, the mixture was stirred under a hydrogen stream for 3 hours at room temperature. After removal of the catalyst by filtration, the filtrate was evaporated to dryness, then dissolved again in a small volume of water, and passed through a column (12 mm in inner diameter) packed with 30 ml of Dowex® 50 W-X4 (H-type). The column was then washed with 90 ml of water and eluted with 0.5 M aqueous ammonia. Fraction Nos. 28 to 34 (each 3 ml in volume) were combined and evaporated to dryness to obtain 201 mg (96% yield) of (S)-7-amino-3-hydroxyheptanamide. [α]D22 -2° (c, 2 water).
Reaction SMILES: Cl.[F:2][C:3]([F:25])([F:24])[C:4]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:5]=1[CH:6]([O:14][CH:15]1[CH2:18][NH:17][CH2:16]1)[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=1.[N-:26]=[C:27]=[O:28]>>[F:25][C:3]([F:2])([F:24])[C:4]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:5]=1[CH:6]([O:14][CH:15]1[CH2:18][N:17]([C:27]([NH:26][CH:4]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:5]2)=[O:28])[CH2:16]1)[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][CH:8]=1
Reactant: Fc1ccc(C(OC2CNC2)c2ccc(Cl)cc2)c(C(F)(F)F)c1
Reactant: [N-]=C=O
Agent: Cl
Product: O=C(NC1CCCCC1)N1CC(OC(c2ccc(Cl)cc2)c2ccc(F)cc2C(F)(F)F)C1

Procedure:
This material was prepared 3-[2-(trifluoromethyl)-4-fluoro-4′-chlorobenzhydryloxy]azetidine hydrochloride (125) and the corresponding isocyanate using the procedure described for compound (10).
Reaction SMILES: [C:1]1([C:7]2([CH2:16][C:17]([OH:19])=[O:18])[CH2:15][CH:14]=[C:10]3[CH:11]=[CH:12][CH:13]=[C:9]3[O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CO.[C:22]1(C)C=CC(S(O)(=O)=O)=CC=1>O>[C:1]1([C:7]2([CH2:16][C:17]([O:19][CH3:22])=[O:18])[CH2:15][CH:14]=[C:10]3[CH:11]=[CH:12][CH:13]=[C:9]3[O:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C(O)CC1(c2ccccc2)CC=C2C=CC=C2O1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Solvent: O
Product: COC(=O)CC1(c2ccccc2)CC=C2C=CC=C2O1
Yield: 228.2 %

Procedure:
A solution of 20.45 g of the product of Step B, 200 ml of methanol and 6 g of p-toluene sulfonic acid was refluxed for one hour and the solution was brought to dryness, then poured into water. Extraction was carried out with methylene chloride and the extracts were dried, filtered and concentrated to obtain 21.33 g of the desired product with a Rf =0.33 (eluant: hexane - methylene chloride (60-40)).
Reaction SMILES: [Si:1]([O:8][CH2:9][C@@H:10]([N:18]([CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])[S:19]([C:22]1[CH:27]=[CH:26][C:25]([CH2:28][O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])=[CH:24][CH:23]=1)(=[O:21])=[O:20])[CH2:11][CH2:12][C:13]([F:17])([F:16])[CH2:14][OH:15])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH3:42][S:43](Cl)(=[O:45])=[O:44].[NH4+].[Cl-]>ClCCl>[CH3:42][S:43]([O:15][CH2:14][C:13]([F:16])([F:17])[CH2:12][CH2:11][C@H:10]([N:18]([S:19]([C:22]1[CH:27]=[CH:26][C:25]([CH2:28][O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:31])[CH3:32])=[CH:24][CH:23]=1)(=[O:20])=[O:21])[CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])[CH2:9][O:8][Si:1]([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2])(=[O:45])=[O:44]
Reactant: CS(=O)(=O)Cl
Reactant: CCCCCN([C@@H](CCC(F)(F)CO)CO[Si](C)(C)C(C)(C)C)S(=O)(=O)c1ccc(CO[Si](C)(C)C(C)(C)C)cc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: ClCCl
Product: CCCCCN([C@@H](CCC(F)(F)COS(C)(=O)=O)CO[Si](C)(C)C(C)(C)C)S(=O)(=O)c1ccc(CO[Si](C)(C)C(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 61.4 %

Procedure:
To a stirred solution of the material from Step 7 (242 mg, 0.38 mmol) in dichloromethane (3.8 mL) at 0° C. were added N,N-diisopropylaethylamine (99 μL, 0.57 mmol) and methanesulfonyl chloride (33 μL, 0.417 mmol). The reaction mixture was stirred at room temperature overnight, poured into saturated aqueous NH4Cl and extracted with dichloromethane (2×). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel using EtOAc-hexanes to afford 167 mg of the title compound. LCMS (M+Na)=738.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][C:11]([OH:13])=[O:12])=[CH:5][CH:4]=1.[Br:14]Br>C(O)(=O)C.O>[Br:14][C:8]1[CH:7]=[C:6]([CH2:9][CH2:10][C:11]([OH:13])=[O:12])[CH:5]=[CH:4][C:3]=1[O:2][CH3:1]
Reactant: BrBr
Reactant: COc1ccc(CCC(=O)O)cc1
Solvent: O
Solvent: CC(=O)O
Product: COc1ccc(CCC(=O)O)cc1Br
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 86.9 %

Procedure:
To a solution of 3-(4-methoxyphenyl)propionic acid (4.0 g, 22.2 mmol) in acetic acid (20 ml) was added bromine (3.9 g, 24.4 mmol) gradually dropwise at 10° C. and the mixture was stirred at room temperature for 30 minutes. This reaction mixture was diluted with water and extracted with ethyl acetate. The extract was washed serially with saturated saline and water and dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane to provide the title compound (yield 5.0 g, 87%).
Reaction SMILES: [N+:1]([CH:4]([CH3:13])[CH:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[OH:6])([O-:3])=[O:2].[C:14](OC(=O)C)(=[O:16])[CH3:15].CO>C(OCC)C.CN(C)C1C=CN=CC=1>[C:14]([O:6][CH:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH:4]([N+:1]([O-:3])=[O:2])[CH3:13])(=[O:16])[CH3:15]
Reactant: CC(C(O)c1ccccc1)[N+](=O)[O-]
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Solvent: CO
Solvent: CCOCC
Product: CC(=O)OC(c1ccccc1)C(C)[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h
Yield: 86 %

Procedure:
To a solution of 2-nitro-1-phenylpropan-1-ol (32 g) and acetic anhydride (22 mL) in diethyl ether (300 mL) was added 4-dimethylaminopyridine (0.61 g) under ice-cooling, and the mixture was stirred at room temperature for 1 hr. Methanol was added to the reaction mixture, and the mixture was further stirred for 30 min and concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound as a yellow oil (yield 34 g, 86%).
Reaction SMILES: S(Cl)([Cl:3])=O.[CH:5]1([O:10][C:11]2[CH:12]=[C:13]([CH:17]=[CH:18][C:19]=2[O:20][CH3:21])[C:14](O)=[O:15])[CH2:9][CH2:8][CH2:7][CH2:6]1>C1(C)C=CC=CC=1>[CH:5]1([O:10][C:11]2[CH:12]=[C:13]([CH:17]=[CH:18][C:19]=2[O:20][CH3:21])[C:14]([Cl:3])=[O:15])[CH2:9][CH2:8][CH2:7][CH2:6]1
Reactant: O=S(Cl)Cl
Reactant: COc1ccc(C(=O)O)cc1OC1CCCC1
Solvent: Cc1ccccc1
Product: COc1ccc(C(=O)Cl)cc1OC1CCCC1
Temperature: 85 °C

Procedure:
Stirring thionyl chloride (20 mL) is treated portionwise with 3-cyclopentyloxy-4-methoxybenzoic acid (5.0 g; that is prepared as described hereinbefore in Reference Example 2) and the solution is then heated at 85° C. for 3 hours. Toluene (50 mL) is added and the mixture is concentrated to give 3-cyclopentyloxy-4-methoxybenzoyl chloride (4.12 g) in the form of an oil which slowly crystallized. [NMR(CDCl3): 1.6-1.7 (m,2H),1.8-1.95(m,4H),1.94-2.05(m,2H),3.94(s,3H),4.85 (m,1H),6.9(d,1H),7.55(d,1H),7.8(q,1); Elemental analysis: C,61.3; H,5.94; Cl,13.9%; Calculated: C,61.3; H,5.94; Cl,13.92%].
Reaction SMILES: Br[C:2]1[S:3][CH:4]=[CH:5][N:6]=1.[NH2:7][C:8]1[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=1.Cl>CCO>[S:3]1[CH:4]=[CH:5][N:6]=[C:2]1[NH:7][C:8]1[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=1
Reactant: Nc1cccc(O)c1
Reactant: Brc1nccs1
Agent: Cl
Solvent: CCO
Product: Oc1cccc(Nc2nccs2)c1
Temperature: 90 °C
Reaction time: 24 h
Yield: 80 %

Procedure:
Following the general procedure for the synthesis of 2-R-5-(thiazol-2-ylamino)phenol, 2-bromothiazole (3.3 mL, 36.6 mmol), 3-aminophenol (3.1 mL, 18.3 mmol) and 37% HCl solution (3.1 mL, 36.6 mmol) in 10% aqueous EtOH solution (30 mL) was stirred at 90° C. for 24 h. The title compound was obtained after purification by flash chromatography on silica gel (hexane:EtOAc 6/4) in 80% yield (2.98 g).
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:8][C:9]1[CH:14]=[CH:13][C:12](B(O)O)=[CH:11][CH:10]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)C>[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:11][CH:10]=1
Reactant: OB(O)c1ccc(Cl)cc1
Reactant: Ic1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: Clc1ccc(-c2ccccc2)cc1
Temperature: 80 °C
Yield: 90 %

Procedure:
To a solution of iodobenzene (102 mg), 4-chlorophenylboronic acid (117 mg), and potassium carbonate (138 mg) in ethanol (3 ml) was added the plated mesh catalyst precursor (12 mm by 14 mm, wire diameter of 0.1 mm, opening of 0.154 mm) prepared in Example 6 and heated for 12 hours at 80° C. The reaction mixture was cooled to room temperature, and the mesh catalyst precursor was taken off from the mixture and washed with ethanol. The solvent was distilled away from the reaction mixture under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane) to give an intended product, 4-chlorobiphenyl quantitatively. The catalyst precursor taken off from the mixture could be recycled at least ten times with an average yield of not less than 90%. The wet-gilded type and the dry-gilded type provided the similar results.