Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[CH2:3]([C:6]1[C:15]([OH:16])=[CH:14][CH:13]=[C:12]2[C:7]=1[CH:8]=[CH:9][CH:10]=[N:11]2)[CH:4]=[CH2:5].[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C)C=O>[CH2:3]([C:6]1[C:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[CH:14][CH:13]=[C:12]2[C:7]=1[CH:8]=[CH:9][CH:10]=[N:11]2)[CH:4]=[CH2:5]
Reactant: C=CCc1c(O)ccc2ncccc12
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C=CCc1c(OCc2ccccc2)ccc2ncccc12
Reaction time: 1 h
Yield: 93.4 %

Procedure:
To a suspension of sodium hydride (60%, 0.7 g, 16.8 mmol) in anhydrous N,N-dimethylformamide (80 ml) was added 5-allyl-quinolin-6-ol (intermediate 5) (2.68 g, 14 mmol) slowly at room temperature. The reaction mixture was stirred for 1 hour, then benzyl bromide (2.57 ml, 21 mmol) was added. The mixture was allowed to stir for 1.5 hrs at room temperature, quenched with water and extracted with methylene chloride. The organic layer was washed with water, dried over anhydrous sodium sulfate and filtered. The solvent was removed under vacuum. Chromatography (30% hexanes-ethyl acetate) afforded 3.6 g (92%) of 5-allyl-6-benzyloxy-quinoline as a light brown oil. MS ESI m/z 276 [M+H]+.
Reaction SMILES: [C:1]12[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=1)[NH:6]C(=O)[O:4][C:2]2=O.[NH2:13][CH2:14][CH2:15][C:16]1[NH:17][CH:18]=[CH:19][N:20]=1>C(O)(C)C.C(OCC)(=O)C>[NH2:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:1]=1[C:2]([NH:13][CH2:14][CH2:15][C:16]1[NH:17][CH:18]=[CH:19][N:20]=1)=[O:4]
Reactant: NCCc1ncc[nH]1
Reactant: O=c1[nH]c2ccccc2c(=O)o1
Solvent: CC(C)O
Solvent: CCOC(C)=O
Product: Nc1ccccc1C(=O)NCCc1ncc[nH]1
Temperature: 25 °C
Yield: 85.8 %

Procedure:
Twenty grams (0.123 mol) of isatoic anhydride were slowly added to a cold (0° C.) solution of 13.5 g (0.122 mol) of 2-(2-aminoethyl)imidazole in 220 ml isopropanol, under nitrogen. The reaction mixture was gradually warmed to room temperature and allowed to react. When the reaction was complete, as indicated by thin layer chromatography, the solution was reduced to dryness under reduced pressure and the resultant residue was redissolved in an ethyl acetate/aqueous sodium bicarbonate mixture. The resulting layers were separated, the organic layer was washed with water and reduced to dryness to provide a solid. This solid was recrystallized from ethanol containing a small amount of hexane to provide 24.1 g of the desired subtitled intermediate (m.p. 180°-185° C.).
Reaction SMILES: [CH3:1][N:2]=[C:3]=[O:4].[NH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:18]3[CH:19]=[C:20]4[O:25][CH2:24][O:23][C:21]4=[CH:22][C:17]=3[CH2:16][C:15]([CH3:26])=[N:14][N:13]=2)=[CH:8][CH:7]=1>CN(C)C=O.O>[CH3:1][NH:2][C:3]([NH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[C:18]3[CH:19]=[C:20]4[O:25][CH2:24][O:23][C:21]4=[CH:22][C:17]=3[CH2:16][C:15]([CH3:26])=[N:14][N:13]=2)=[CH:8][CH:7]=1)=[O:4]
Reactant: CN=C=O
Reactant: CC1=NN=C(c2ccc(N)cc2)c2cc3c(cc2C1)OCO3
Solvent: CN(C)C=O
Solvent: O
Product: CNC(=O)Nc1ccc(C2=NN=C(C)Cc3cc4c(cc32)OCO4)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 71.1 %

Procedure:
0.8 ml (13.4 mmol) of methyl isocyanate was added to a solution containing 1.0 g (3.41 mmol) of 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine in 8 ml of dimethylformamide (DMF), then the reaction mixture was stirred at 25° C. for 24 hours. After diluting with 80 ml of water, filtering at 5° C. and drying at 60 to 100° C., 1.06 g of raw product, m.p.: 204°-207° C. (sintering from 160° C.) were obtained which, when recrystallized from 5 ml of ethanol, gave 0.85 g (71.4%) of-the aimed product, m.p.: 223°-224° C. (decomp.).
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@H:9]([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])[C@@H:8]([CH2:20][O:21][Si](C(C)(C)C)(C)C)[C@H:7]([O:29][CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][O:31]2)[CH2:6]1)(=[O:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[C:1]([O:4][C@@H:5]1[C@H:9]([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])[C@@H:8]([CH2:20][OH:21])[C@H:7]([O:29][CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][O:31]2)[CH2:6]1)(=[O:3])[CH3:2]
Reactant: COC(=O)CCCCCC[C@@H]1[C@@H](CO[Si](C)(C)C(C)(C)C)[C@H](OC2CCCCO2)C[C@@H]1OC(C)=O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: COC(=O)CCCCCC[C@@H]1[C@@H](CO)[C@H](OC2CCCCO2)C[C@@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 20.5 h
Yield: 98.1 %

Procedure:
A solution of methyl 7-[(1R,2S,3R,5S)-5-acetoxy-2-(t-butyldimethylsilyloxymethyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (27) (118.7 g, 230.6 mmol) in tetrahydrofuran (450 ml) was cooled on ice. A solution of 1M-tetra butyl ammonium fluoride (in THF, 277 ml, 277 mmol) was added drop wise thereto and the mixture was stirred at room temperature for 20.5 hours. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (Fuji Silysia BW-300: 2000 g; ethyl acetate:hexane=1:1). The fractions containing impurities were re-purified by silica gel column chromatography (Fuji Silysia BW-300: 520 g; ethyl acetate:hexane=1:1) to give methyl 7-[(1R,2S,3R,5S)-5-acetoxy-2-hydroxymethyl-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (28) (90.64 g, 226.3 mmol, 98.1%) as colorless oil.
Reaction SMILES: [Br-].[CH:2]([S:15][C:16](N)=[NH2+])([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.ClC[C:21]([NH2:23])=[O:22]>>[CH:2]([S:15][CH2:16][C:21]([NH2:23])=[O:22])([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: NC(=[NH2+])SC(c1ccccc1)c1ccccc1
Reactant: NC(=O)CCl
Agent: [Br-]
Product: NC(=O)CSC(c1ccccc1)c1ccccc1

Procedure:
In Steps 2 and 3, the S-benzhydrylthiouronium bromide formed in step 1 is converted to the corresponding thiol, and then reacted with chloroacetamide to form 2-(benzhydrylthiyl)acetamide. For example, the thiourea can be converted to the thiol by reaction with a suitable base. The reaction steps 2 and 3 can be carried out in the same reaction vessel as was employed in step 1, without isolation of any intermediates.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:18](OC)=[O:19])[CH2:17][CH2:16][C:11]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.ClCCl.CC(C[AlH]CC(C)C)C.S([O-])([O-])(=O)=O.[Mg+2]>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:18][OH:19])[CH2:9][CH2:10][C:11]3([O:12][CH2:13][CH2:14][O:15]3)[CH2:16][CH2:17]2)=[CH:4][CH:3]=1
Reactant: COC(=O)C1(c2ccc(Br)cc2)CCC2(CC1)OCCO2
Agent: CC(C)C[AlH]CC(C)C
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: OCC1(c2ccc(Br)cc2)CCC2(CC1)OCCO2
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
To a round bottom flask containing methyl 8-(4-bromophenyl)-1,4-dioxaspiro[4.5]decane-8-carboxylate (5.30 g, 14.92 mmol) was added anhydrous dichloromethane (60 ml) at room temperature. The content was then cool to −78° C. under a dry ice-acetone bath and DIBAL-H (31.1 ml, 37.30 mmol) in toluene was added dropwise slowly. When the addition was completed, the mixture was stirred at −78° C. for 30 minutes or until the consumption of the starting material as indicated by thin layer chromatography (TLC). The reaction was then quenched by the slow addition of a pH 8 buffered solution (prepared by mixing 0.53 mL ammonium hydroxide solution and 8.8 mL of saturated ammonium chloride solution) at −78° C. The mixture was then allowed to warm back up to room temperature and stirred for a further 45 minutes. Solid magnesium sulfate (8 g) was added and the mixture stirred at room temperature for another 30 minutes to afford free flowing slurry. The content was filtered and concentrated to afford the title compound as clear oil, which was used in the next step without purification (4.88 g). LC/MS, ESI-MS: non-ionizable, RT: 1.05 (Condition E).
Reaction SMILES: [N:1]1([CH2:6][C:7](=[O:14])[C:8]([CH3:13])([CH3:12])[CH:9]([CH3:11])[CH3:10])[CH:5]=[N:4][CH:3]=[N:2]1.[OH-].[K+].[Cl:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Br)=[CH:20][CH:19]=1>CS(C)=O.O>[CH3:11][CH:9]([C:8]([CH3:12])([CH3:13])[C:7](=[O:14])[CH:6]([N:1]1[CH:5]=[N:4][CH:3]=[N:2]1)[CH2:22][C:21]1[CH:24]=[CH:25][C:18]([Cl:17])=[CH:19][CH:20]=1)[CH3:10]
Reactant: CC(C)C(C)(C)C(=O)Cn1cncn1
Reactant: Clc1ccc(CBr)cc1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CS(C)=O
Product: CC(C)C(C)(C)C(=O)C(Cc1ccc(Cl)cc1)n1cncn1
Temperature: 100 °C
Reaction time: 15 h
Yield: 67.6 %

Procedure:
15.6 g (0.08 mol) of 1-(1,2,4-triazol-1-yl)-3,3,4-trimethylpentan-2-one are dissolved in 100 ml of dimethylsulphoxide, and 4.5 g (0.08 mol) of potassium hydroxide, dissolved in 10 ml of water, are added, while cooling. 16.4 g (0.08 mol) of 4-chlorobenzyl bromide, dissolved in 50 ml of dimethylsulphoxide, are added dropwise to the mixture at a rate such that the temperature does not exceed 40° C. Thereafter, the mixture is slowly warmed to 100° C. and stirred for a further 15 hours at this temperature, and the cooled solution is poured onto 500 ml of water. The mixture is extracted with twice 250 ml of methylene chloride, the methylene chloride phase is then extracted with four times 100 ml of water, and the organic phase is evaporated down. The residue is taken up in 100 ml of acetone, and 14.4 g of naphthalene-1,5-disulphonic acid, dissolved in 50 ml of acetone, are added. The 2,3,3-trimethyl-5-(1,2,4-triazol-1-yl)-6-(4-chlorophenyl)-hexan-3-one salt of naphthalene-1,5-disulphonic acid crystallizes out. The precipitate is filtered off under suction and taken up in 250 ml of saturated sodium bicarbonate solution, the aqueous phase is extracted with four times 100 ml of methylene chloride, the methylene chloride phase is extracted with 100 ml of water, and the solvent is distilled off from the organic phase. 17.3 g (67.6% of theory) of 2,3,3-trimethyl-5-(1,2,4-triazol-1-yl)-6-(4-chlorophenyl)-hexan-4-one are obtained as colorless crystals of melting point 91°-94° C.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[O:5][C:6]1[C:15]2[NH:14][C:13](=[O:16])[CH:12]=[N:11][C:10]=2[N:9]=[CH:8][CH:7]=1.[C:20]([C:24]1[CH:28]=[C:27]([N:29]=[C:30]=[O:31])[N:26]([C:32]2[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=2)[N:25]=1)([CH3:23])([CH3:22])[CH3:21]>>[C:20]([C:24]1[CH:28]=[C:27]([NH:29][C:30]([NH:1][C:2]2[CH:19]=[CH:18][CH:17]=[C:4]([O:5][C:6]3[C:15]4[NH:14][C:13](=[O:16])[CH:12]=[N:11][C:10]=4[N:9]=[CH:8][CH:7]=3)[CH:3]=2)=[O:31])[N:26]([C:32]2[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=2)[N:25]=1)([CH3:23])([CH3:22])[CH3:21]
Reactant: Nc1cccc(Oc2ccnc3ncc(=O)[nH]c23)c1
Reactant: Cc1ccc(-n2nc(C(C)(C)C)cc2N=C=O)cc1
Product: Cc1ccc(-n2nc(C(C)(C)C)cc2NC(=O)Nc2cccc(Oc3ccnc4ncc(=O)[nH]c34)c2)cc1

Procedure:
Method F2 was used with 8-(3-aminophenoxy)pyrido[2,3-b]pyrazin-2(1H)-one and 3-tert-butyl-5-isocyanato-1-p-tolyl-1H-pyrazole to afford the title compound as a slightly yellow solid (9 mg, 13%).
Reaction SMILES: [CH2:1]([O:3][P:4]([C:9]([P:11](=[O:18])([O:15][CH2:16][CH3:17])[O:12][CH2:13][CH3:14])=[CH2:10])(=[O:8])[O:5][CH2:6][CH3:7])[CH3:2].[N+:19](=[CH:21][C:22](=[O:38])[CH:23]([C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[C:27]([F:37])[CH:26]=1)[CH3:24])=[N-:20]>CCOCC>[CH2:16]([O:15][P:11]([C:9]1([P:4](=[O:8])([O:5][CH2:6][CH3:7])[O:3][CH2:1][CH3:2])[CH2:10][C:21]([C:22](=[O:38])[CH:23]([C:25]2[CH:30]=[CH:29][C:28]([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)=[C:27]([F:37])[CH:26]=2)[CH3:24])=[N:19][NH:20]1)(=[O:18])[O:12][CH2:13][CH3:14])[CH3:17]
Reactant: C=C(P(=O)(OCC)OCC)P(=O)(OCC)OCC
Reactant: CC(C(=O)C=[N+]=[N-])c1ccc(-c2ccccc2)c(F)c1
Solvent: CCOCC
Product: CCOP(=O)(OCC)C1(P(=O)(OCC)OCC)CC(C(=O)C(C)c2ccc(-c3ccccc3)c(F)c2)=NN1

Procedure:
Ethenylidene bisphosphonic acid tetraethyl ester (II, PREPARATION 1, 11.1 g) and 1-diazo-3-[2-fluoro(1,1'-biphenyl)-4-yl]-butan-2-one (I, PREPARATION 3, 10.0 g) are stirred for 18 hrs in ether (40 ml). A seed crystal from an earlier reaction is added to the mixture, whereupon the reaction sets up into a solid mass. The precipitate is filtered, then recrystallized from methylene chloride/hexane (45/55) to give the title compound, mp 109°-110°; MS (m/e) 568, 431, 403, 385, 341, 313, 301 and 199; IR (mineral oil mull) 3179, 1656, 1557, 1265, 1246, 1033, 1009, 993, 976 and 965 cm-1 ; NMR (CDCl3) 7.4, 7.2, 6.91, 4.81, 4.4, 4.05, 3.4, 1.49, 1.34, 1.16 and 1.08 δ; CMR (CDCl3) 195.1, 162, 158, 149, 142, 136, 130.7, 128.8, 128.5, 127.6, 123.9, 115.8, 115.6, 64.3, 63.6, 46.1, 36.4, 17.7, 16.5, 16.2 and 16.1 δ.
Reaction SMILES: [CH2:1]([N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:15]([O:17][CH3:18])=[O:16])[CH:13]=2)[NH:8][CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4].C(N(CC)CC)C.[CH3:26][S:27](Cl)(=[O:29])=[O:28]>C(Cl)Cl>[CH2:1]([N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([C:15]([O:17][CH3:18])=[O:16])[CH:13]=2)[N:8]([S:27]([CH3:26])(=[O:29])=[O:28])[CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCN1CCNc2ccc(C(=O)OC)cc21
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCN1CCN(S(C)(=O)=O)c2ccc(C(=O)OC)cc21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To an ice-cold, stirred solution of methyl 4-butyl-1,2,3,4-tetrahydroquinoxaline-6-carboxylate (180 mg) and triethylamine (62 μL) in methylene chloride (2 mL) was added methanesulfonyl chloride (101 μL) and the mixture was stirred for 1 h. The mixture was warmed to room temperature, diluted with methylene chloride, washed with washed with 1 N hydrochloric acid, and brine. The organic layer was then dried (magnesium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica, 1:3 ethyl acetate/hexanes) provided 150 mg of the title compound: 1H NMR (300 MHz, CDCl3) δ 7.57, 7.41, 7.32, 3.90, 3.84, 3.45, 3.38, 1.61, 1.41, 0.98.
Reaction SMILES: [H-].[Na+].CN(C)C=O.[CH3:8][C:9]1[C:10](=[O:22])[NH:11][C:12]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:13][C:14]=1[CH3:15].Br[CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26]>C(Cl)(Cl)Cl>[CH3:8][C:9]1[C:10]([O:22][CH2:24][C:25]([O:27][CH2:28][CH3:29])=[O:26])=[N:11][C:12]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[N:13][C:14]=1[CH3:15]
Reactant: CCOC(=O)CBr
Reactant: Cc1nc(-c2ccccc2)[nH]c(=O)c1C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClC(Cl)Cl
Product: CCOC(=O)COc1nc(-c2ccccc2)nc(C)c1C
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 86.7 %

Procedure:
To a mixture of sodium hydride (about 60% oily, 1.0 g) and dimethylformamide (80 ml) is added 5,6-dimethyl-2-phenyl-4(3H)-pyrimidinone (5.0 g) while the temperature of the mixture is kept at 0-5° C., and the mixture is stirred at 0° C. for 30 minutes. To the mixture is added dropwise ethyl bromoacetate (4.2 g) at the same temperature. After addition, the mixture is stirred at 80° C. for three hours, and thereto are added ice-water and chloroform. The chloroform layer is collected by filtration, washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (eluent; chloroform), and recrystallized from isopropanol to give ethyl 2-(5,6-dimethyl-2-phenyl-4-pyrimidinyloxy)acetate (6.2 g), m.p. 90-91° C.
Reaction SMILES: [CH2:1]([C:5]1[NH:6][C:7]([CH:11]=[O:12])=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4].C(=O)([O-])[O-].[K+].[K+].[I:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24]Br)=[CH:22][CH:21]=1>CN(C)C=O>[CH2:1]([C:5]1[N:6]([CH2:24][C:23]2[CH:26]=[CH:27][C:20]([I:19])=[CH:21][CH:22]=2)[C:7]([CH:11]=[O:12])=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc(Cl)c(C=O)[nH]1
Reactant: BrCc1ccc(I)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCc1nc(Cl)c(C=O)n1Cc1ccc(I)cc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A mixture of 2-butyl-4-chloro-1H-imidazole-5-carboxaldehyde (4.0 g; preparable as described in Drugs of the Future (1991), Vol. 16, p 305), potassium carbonate (2.94 g) and dry dimethylformamide (50 ml) was stirred for 15 minutes at ambient temperature. 4-Iodobenzyl bromide (6.34 g) was added to the resulting mixture and stirring was continued for approximately 17 hours. The solvent was then evaporated under reduced pressure at 80° C. Water (200 ml) was added to the resulting residue which was then extracted with diethyl ether (2×100 ml). The combined extracts were washed with water (50 ml) and dried over magnesium sulphate. The solvent was evaporated. The resulting residue was purified by flash chromatography on silica gel (eluting with dichloromethane/methanol (80:1)) to give the intermediate compound 2-butyl-4-chloro-1-(4-iodobenzyl)-1H-imidazole-5-carboxaldehyde as an oil (6.9 g).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[CH2:5][NH:6][CH3:7].CCN(C(C)C)C(C)C.[C:20](Cl)(=[O:22])[CH3:21]>CN(C)C1C=CN=CC=1.CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[CH2:5][N:6]([CH3:7])[C:20](=[O:22])[CH3:21]
Reactant: CNCc1cccc(Br)c1
Reactant: CC(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(=O)N(C)Cc1cccc(Br)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a DMF (0.1 M) solution of 3-bromo-N-methylbenzylamine (1 eq.), Hunig's base (3 eq) and 4-(dimethylamino)pyridine (5% loading) was added acetyl chloride (1.5 eq). The resulting reaction mixture was stirred at RT for 16 h. After quenching the reaction with sat. aq. NaHCO3, the mixture was extracted with EtOAc. The organic extract was washed with 10% aq. HCl, sat. aq. NaHCO3, and brine. Drying over Na2SO4, filtration and concentration of the filtrate in vacuo afforded the crude product as a yellow oil. Purification by way of flash chromatography (SiO2, 4:1 (v/v) Hex:EtOAc→EtOAc) afforded the title compound as a yellow oil.
Reaction SMILES: [CH3:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][CH:7]([CH3:17])[CH2:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15]O)=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.C(Cl)(Cl)(Cl)[Cl:21].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>C1COCC1>[CH3:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][CH:7]([CH3:17])[CH2:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][Cl:21])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1
Reactant: Cc1ccc(OC(C)Cc2ccc(CO)cc2)cc1
Reactant: ClC(Cl)(Cl)Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Cc1ccc(OC(C)Cc2ccc(CCl)cc2)cc1
Temperature: 25 °C

Procedure:
To a solution of {4-[2-(4-methylphenoxy)propyl]phenyl}methanol (0.725 g) in THF (20 mL) were added CCl4 (2.3 mL) and PPh3 (1.640 g) at room temperature under an Ar atmosphere. The mixture was heated at reflux for 6.5 hours, and then cooled to room temperature, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/AcOEt=5/1) to afford 1-[4-(chloromethyl)phenyl]propan-2-yl 4-methylphenyl ether (0.696 g) as a colorless oil.