Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([O:7][C:8]2[CH:16]=[CH:15][C:11]([C:12](O)=[O:13])=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.B.Cl>O1CCCC1>[C:1]1([O:7][C:8]2[CH:16]=[CH:15][C:11]([CH2:12][OH:13])=[CH:10][CH:9]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C(O)c1ccc(Oc2ccccc2)cc1
Agent: B
Agent: Cl
Solvent: C1CCOC1
Product: OCc1ccc(Oc2ccccc2)cc1
Reaction time: 8 h
Yield: 87.3 %

Procedure:
To a solution of 4-(phenyloxy)benzoic acid (10.4 g, 48.7 mmol) in tetrahydrofuran (30 ml) was added 1M tetrahydrofuran solution of borane (63 ml, 63 mmol) at room temperature and the mixture was stirred overnight. 1N Hydrochloric acid was added to the reaction solution for quenching and the mixture was extracted with ethyl acetate (100 ml×2). The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate) and recrystallized from hexane to give (4-(phenyloxy)phenyl)methanol (8.51 g, 87%).
Reaction SMILES: [CH:1]1([C:4]2[CH:27]=[CH:26][C:7]([C:8]([N:10]([C@@H:12]3[CH2:17][CH2:16][NH:15][CH2:14][C@H:13]3[C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=3)[CH3:11])=[O:9])=[CH:6][CH:5]=2)[CH2:3][CH2:2]1.[CH3:28][S:29]([N:32]1[CH2:37][CH2:36][CH:35]([C:38](O)=[O:39])[CH2:34][CH2:33]1)(=[O:31])=[O:30]>>[CH:1]1([C:4]2[CH:27]=[CH:26][C:7]([C:8]([N:10]([C@@H:12]3[CH2:17][CH2:16][N:15]([C:38]([CH:35]4[CH2:36][CH2:37][N:32]([S:29]([CH3:28])(=[O:31])=[O:30])[CH2:33][CH2:34]4)=[O:39])[CH2:14][C@H:13]3[C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=3)[CH3:11])=[O:9])=[CH:6][CH:5]=2)[CH2:3][CH2:2]1
Reactant: CN(C(=O)c1ccc(C2CC2)cc1)[C@@H]1CCNC[C@H]1c1ccc(Cl)c(Cl)c1
Reactant: CS(=O)(=O)N1CCC(C(=O)O)CC1
Product: CN(C(=O)c1ccc(C2CC2)cc1)[C@@H]1CCN(C(=O)C2CCN(S(C)(=O)=O)CC2)C[C@H]1c1ccc(Cl)c(Cl)c1

Procedure:
Using the compound obtained in step 1 and 1-(methylsulfonyl)piperidine-4-carboxylic acid, and by the reaction and purification in the same manner as in Example 97, the title compound was obtained.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([OH:10])=[O:9])[CH:3]=1.S(=O)(=O)(O)O.[CH3:16]O>>[CH3:16][O:9][C:8](=[O:10])[C:4]1[CH:3]=[C:2]([I:1])[CH:7]=[CH:6][N:5]=1
Reactant: CO
Reactant: O=C(O)c1cc(I)ccn1
Agent: O=S(=O)(O)O
Product: COC(=O)c1cc(I)ccn1
Temperature: 25 °C
Yield: 90 %

Procedure:
To a solution of 4-iodopicolinic acid 11a (7.0 g, 18.6 mmol) in MeOH (70 mL) at 23° C. was added concentrated sulfuric acid (350 μL), and the reaction mixture was refluxed for 48 h. The reaction mixture was cooled to room temperature and concentrated to yield the desired product 4-iodopicolinic acid methyl ester 11b (4.4 g, 90%) as a yellow oil; 1H NMR (300 MHz, CDCl3) δ 8.52 (t, J=0.6, 1.5, 1), 8.40 (d, J=5.1, 1), 7.86–7.88 (dd, J=0.6, 5.1, 1), 4.02 (s, 3); MS (ESPOS): 263.9 [M+H]; 285.9 [M+Na].
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=[O:11])=[CH:5][CH:4]=1.[Li]CCCC.[CH3:18][O:19][C:20]1[CH:21]=[C:22]([CH2:26][CH2:27]Br)[CH:23]=[CH:24][CH:25]=1>C1COCC1.CCCCCC>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]([CH2:27][CH2:26][C:22]2[CH:23]=[CH:24][CH:25]=[C:20]([O:19][CH3:18])[CH:21]=2)[C:10]([OH:12])=[O:11])=[CH:7][CH:8]=1
Reactant: COc1cccc(CCBr)c1
Reactant: COc1ccc(CC(=O)O)cc1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: COc1ccc(C(CCc2cccc(OC)c2)C(=O)O)cc1
Temperature: -70 °C
Reaction time: 1.5 h

Procedure:
4-Methoxyphenylacetic acid (50.68 g, 305 mmol) was dissolved in 1.4 L of THF and cooled to -70° C. under a nitrogen atmosphere. 400 mL of 1.6M (640.5 mmol) of n-BuLi in hexane was slowly added. 72.1 g (335.5 mmol) of 2-(3-methoxyphenyl)ethylbromide in 400 mL of THF was slowly added and the reaction allowed to proceed for 1.5 hours. The reaction was allowed to warm to ambient temperature. The reaction was quenched with 500 mL of 0.5N NaOH and heated to 50° C. for one hour and cooled to ambient temperature. The reaction mixture was extracted three times with ether, the aqueous layer was acidified with 150 mL of 5N HCl and extracted twice with CHCl3. The CHCl3 extract was washed twice with brine, dried with Na2SO4, and evaporated to a yellow solid. This yielded 78.2 g of the title compound.
Reaction SMILES: F[C:2]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[CH:16]=[CH:15][C:11]2[O:12][CH2:13][O:14][C:10]=2[CH:9]=1)=[O:5].[NH2:24][C@H:25]1[CH2:30][CH2:29][C@H:28]([OH:31])[CH2:27][CH2:26]1>N1C=CC=CC=1>[OH:31][C@H:28]1[CH2:29][CH2:30][C@H:25]([NH:24][C:2]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][C:3]=2[C:4]([NH:6][CH2:7][C:8]2[CH:16]=[CH:15][C:11]3[O:12][CH2:13][O:14][C:10]=3[CH:9]=2)=[O:5])[CH2:26][CH2:27]1
Reactant: N[C@H]1CC[C@H](O)CC1
Reactant: O=C(NCc1ccc2c(c1)OCO2)c1cc([N+](=O)[O-])ccc1F
Solvent: c1ccncc1
Product: O=C(NCc1ccc2c(c1)OCO2)c1cc([N+](=O)[O-])ccc1N[C@H]1CC[C@H](O)CC1
Temperature: 25 °C
Reaction time: 15 h

Procedure:
To a solution of 2-fluoro-5-nitro-N-(1,3-benzodioxol-5-ylmethyl)benzamide (150 mg) in anhydrous pyridine (3 mL) was added trans-4-aminocyclohexanol (81.4 mg), and the mixture was stirred for 15 hours at ambient temperature, and then for 3 hours at 60° C. The mixture was partitioned between ethyl acetate and water. The separated organic layer was washed with water and brine, dried over magnesium sulfate and evaporated in vacuo. The residue was subjected to a silica gel column chromatography eluting with a mixture of chloroform and methanol (20:1). The eluent was concentrated and the residue was triturated with diisopropyl ether to give 2-(trans-4-hydroxycyclohexylamino)-5-nitro-N-(1,3-benzodioxol-5-ylmethyl)benzamide as yellow powders (164 mg).
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][C:5]([Cl:11])=[CH:4][N:3]=1>[Ni].CO>[NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][C:5]([Cl:11])=[CH:4][N:3]=1
Reactant: Nc1ncc(Cl)cc1[N+](=O)[O-]
Agent: [Ni]
Solvent: CO
Product: Nc1cc(Cl)cnc1N
Reaction time: 3 h
Yield: 96.5 %

Procedure:
A mixture of the nitropyridine 2 (22.0 g 126.8 mmol), Raney Ni (2.2 g) and MeOH (220 mL) was shaken under H2 (20-40 psi) for 3 h, then filtered. The filtrate was rota-evaporated and the residual solid was dried to give 17.57 g (96%) of 3 as a tan powder, mp 169°-171° C. (lit. 172°-173° C., (Israel, M. & Day, A. R., J. Org. Chem. 24:1455-1460 (1959))). 1H NMR (DMSO-d6), 4.991 (bs, 2H), 5.555 (bs, 2H), 6.675 (d, 1H, J=2), 7.196 (d, 1H, J=2).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:20][C:21]([OH:23])=O)[CH:6]=[CH:7][C:8]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19])=[O:11].[CH:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][C:25]=1[O:34][C@@H:35]1[CH2:39][NH:38][C@H:37]([CH2:40][O:41][C:42]2[CH:51]=[CH:50][C:45]([C:46]([O:48][CH3:49])=[O:47])=[CH:44][CH:43]=2)[CH2:36]1.CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:20][C:21]([N:38]2[CH2:39][C@@H:35]([O:34][C:25]3[CH:26]=[CH:27][C:28]4[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=4)[CH:24]=3)[CH2:36][C@H:37]2[CH2:40][O:41][C:42]2[CH:43]=[CH:44][C:45]([C:46]([O:48][CH3:49])=[O:47])=[CH:50][CH:51]=2)=[O:23])[CH:6]=[CH:7][C:8]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19])=[O:11]
Reactant: COC(=O)c1ccc(OC[C@@H]2C[C@H](Oc3ccc4ccccc4c3)CN2)cc1
Reactant: COc1cc(CC(=O)O)ccc1NC(=O)Nc1ccccc1C
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(OC[C@@H]2C[C@H](Oc3ccc4ccccc4c3)CN2C(=O)Cc2ccc(NC(=O)Nc3ccccc3C)c(OC)c2)cc1
Temperature: 25 °C
Reaction time: 72 h
Yield: 728.1 %

Procedure:
A mixture of 3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetic acid (333 mg, 0.106 mmol), methyl 4-[(2S, 4S)4-(2-naphthyloxy)-2-pyrrolidinyl]methoxybenzoate (400 mg, 1.06 mmol), EDC.HCl (305 mg, 1.59 mmol) and DMAP (194 mg, 1.59 mmol) in DMF (10 ml) was stirred at room temperature for 3 days. The mixture was poured into ice water and extracted with EtOAc. The combined extracts were washed with ice water and brine. After dried over Na2SO4, the extracts were concentrated in vacuo. The residue was chromatographed on silica gel [100 g, n-hexane/EtOAc(1/1)CHCl3/MeOH(50/1)], to give methyl 4-[(2S, 4S)-1-[3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetyl]-4-(2-naphthyloxy)-2-pyrrolidinyl]methoxybenzoate (520 mg, 73%) as a pale brown amorphous. 1H-NMR (CDCl3) δ 2.28 (s, 3H), 2.29 (m, 1H), 2.55 (d, J=14.2 Hz, 1H), 3.60 (d, J=3.4 Hz, 2H), 3.66 (d, J=3.7 Hz, 3H), 3.68–4.00 (m, 5H), 4.05–4.67 (m, 3H), 5.09 (br, 1H), 6.61 (s, 1H), 6.77 (m, 2H), 6.87 (d, J=8.8 Hz, 1H), 6.94–7.54 (m, 8H), 7.68–8.09 (m, 8H); MS (ESI) m/z 674 (M++1).
Reaction SMILES: [C:1]1([NH:7][C:8]2([C:21]#[N:22])[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(=O)(=O)(O)[OH:24].[OH-].[NH4+]>FC(F)(F)C(O)=O>[C:1]1([NH:7][C:8]2([C:21]([NH2:22])=[O:24])[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:10][CH2:9]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=S(=O)(O)O
Reactant: N#CC1(Nc2ccccc2)CCN(Cc2ccccc2)CC1
Agent: [NH4+]
Agent: [OH-]
Solvent: O=C(O)C(F)(F)F
Product: NC(=O)C1(Nc2ccccc2)CCN(Cc2ccccc2)CC1
Temperature: 47.5 °C
Reaction time: 16 h
Yield: 82 %

Procedure:
Aminonitrile 1 (2.0 g, 6.86 mmol) was dissolved in 11 mL of trifluoroacetic acid under a nitrogen atmosphere. Sulfuric acid (2.7 mL) was added dropwise. The light brown solution was stirred at 45-50° C. for 16 h. The reaction mixture was cooled to room temperature and slowly poured into an ammonium hydroxide 40 mL/ice mixture. The solution was filtered and the solids were collected to give 1.73 g of amide 2 in an 82% yield. mp 179-182° C.; 1H NMR (CDCl3) δ 7.33-7.16 (m, 5H), 6.89 (br s, 1H), 6.78 (t, 1H, J=7.33 Hz), 6.63 (d, 2H, J=7.33 Hz), 5.48 (s, 1H), 4.05 (s, 1H), 2.77-2.71 (m, 2H), 2.37-2.30 (m, 2H), 2.10 (t, 2H, J=11.91 Hz), 1.95 (br d, 2H, J=13.28 Hz); 13C NMR (CDCl3) 178.7, 143.8, 138.3, 129.3, 129.1, 129.0, 128.3, 127.2, 119.3, 116.2, 63.1, 58.3, 48.8, 31.4.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]2[C:21]([N+:22]([O-:24])=[O:23])=[CH:20][N:19]=[C:18](Cl)[CH:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:26][C:27]([F:38])([F:37])[O:28][C:29]1[CH:36]=[CH:35][CH:34]=[CH:33][C:30]=1[CH2:31][NH2:32].C(N(C(C)C)CC)(C)C>CC(N(C)C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]2[C:21]([N+:22]([O-:24])=[O:23])=[CH:20][N:19]=[C:18]([NH:32][CH2:31][C:30]3[CH:33]=[CH:34][CH:35]=[CH:36][C:29]=3[O:28][C:27]([F:26])([F:37])[F:38])[CH:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: NCc1ccccc1OC(F)(F)F
Reactant: CC(C)(C)OC(=O)N1CCC(CNc2cc(Cl)ncc2[N+](=O)[O-])CC1
Solvent: CC(=O)N(C)C
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N1CCC(CNc2cc(NCc3ccccc3OC(F)(F)F)ncc2[N+](=O)[O-])CC1
Temperature: 100 °C
Reaction time: 18 h
Yield: 64.1 %

Procedure:
The 4-[(2-chloro-5-nitro-pyridin-4-ylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl ester (100 mg, 0.27 mmol) was dissolved in DMA (5.0 mL). 2-Trifluoromethoxybenzyl amine (153 mg, 0.80 mmol) was added followed by diisopropylethylamine (0. 14 mL, 0.80 mmol). The reaction was heated to 100° C. and stirred for 18 h, then cooled to 25° C. The volatiles were removed in vacuo and the crude product was purified by flash column chromatography (SiO2, 15-50% EtOAc-hexanes) to afford 4-{[5-nitro-2-(2-trifluoromethoxy-benzylamino)-pyridin-4-ylamino]-methyl}-piperidine-1-carboxylic acid tert-butyl ester as a yellow foam (91 mg, 64%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([C:15]([OH:17])=O)=[CH:11][CH:10]=1.[NH2:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]2[CH2:29][CH2:28][CH:27]([N:30]([CH3:32])[CH3:31])[CH2:26]2)=[CH:21][CH:20]=1>>[CH3:31][N:30]([CH3:32])[CH:27]1[CH2:28][CH2:29][N:25]([C:22]2[CH:23]=[CH:24][C:19]([NH:18][C:15]([C:12]3[CH:11]=[CH:10][C:9]([C:3]4[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=4[F:1])=[CH:14][CH:13]=3)=[O:17])=[CH:20][CH:21]=2)[CH2:26]1
Reactant: O=C(O)c1ccc(-c2ccc(F)cc2F)cc1
Reactant: CN(C)C1CCN(c2ccc(N)cc2)C1
Product: CN(C)C1CCN(c2ccc(NC(=O)c3ccc(-c4ccc(F)cc4F)cc3)cc2)C1

Procedure:
2′,4′-Difluorobiphenyl-4-carboxylic acid was reacted with [1-(4-aminophenyl)pyrrolidin-3-yl]dimethylamine by method E-a. This resulted in the product with the molecular weight of 421.20 (C25H25F2N3O); MS (ESI): 422 (M+H+) as hydrotrifluoroacetate.
Reaction SMILES: C(C1C=CC(C2ON=[C:13]3[C:16]4[C:21]([CH2:22][CH2:23][C:12]=23)=[CH:20][C:19]([CH:24]=[O:25])=[CH:18][CH:17]=4)=CC=1C(F)(F)F)C(C)C.[CH3:30][N:31]1[C:39]([C:40]2[C:44]([C:45]([F:48])([F:47])[F:46])=[C:43]([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[O:42][N:41]=2)=C2C(C3C=CC(C=C)=CC=3CC2)=[N:32]1>>[CH3:30][N:31]1[C:39]([C:40]2[C:44]([C:45]([F:47])([F:46])[F:48])=[C:43]([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[O:42][N:41]=2)=[C:12]2[C:13]([C:16]3[CH:17]=[CH:18][C:19]([CH:24]=[O:25])=[CH:20][C:21]=3[CH2:22][CH2:23]2)=[N:32]1
Reactant: C=Cc1ccc2c(c1)CCc1c-2nn(C)c1-c1noc(-c2ccccc2)c1C(F)(F)F
Reactant: CC(C)Cc1ccc(-c2onc3c2CCc2cc(C=O)ccc2-3)cc1C(F)(F)F
Product: Cn1nc2c(c1-c1noc(-c3ccccc3)c1C(F)(F)F)CCc1cc(C=O)ccc1-2

Procedure:
This compound was prepared according to the general procedure described for Preparation 23D, employing 240 mgs of 3-(2-methyl-7-vinyl-4,5-dihydro-2H-benzo[g]indazol-3-yl)-5-phenyl-4-(trifluoromethyl)isoxazole (79B). Yield: 235 mgs (97%); LC/MS M+1=424.2.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([CH:13]([CH3:15])[CH3:14])=[N:10][C:9]=2[C:16]2[CH:17]=[CH:18][C:19]([F:33])=[C:20]([NH:22][S:23]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=3)(=[O:25])=[O:24])[CH:21]=2)[CH:5]=[CH:4][N:3]=1.[NH3:34]>CO>[NH2:34][C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]([CH:13]([CH3:15])[CH3:14])=[N:10][C:9]=2[C:16]2[CH:17]=[CH:18][C:19]([F:33])=[C:20]([NH:22][S:23]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[CH:27]=3)(=[O:25])=[O:24])[CH:21]=2)[CH:5]=[CH:4][N:3]=1
Reactant: N
Reactant: CC(C)c1nc(-c2ccc(F)c(NS(=O)(=O)c3cccc(F)c3)c2)c(-c2ccnc(Cl)n2)s1
Solvent: CO
Product: CC(C)c1nc(-c2ccc(F)c(NS(=O)(=O)c3cccc(F)c3)c2)c(-c2ccnc(N)n2)s1

Procedure:
Following a procedure analogous to the procedure described in Example 51, Step B using N-{5-[5-(2-chloro-4-pyrimidinyl)-2-(1-methylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-3-fluorobenzenesulfonamide (100 mg, 0.20 mmol) and 7 N ammonia in MeOH (2 mL) the title compound was obtained as a white powder (46 mg, 0.09 mmol, 47.2% yield). 1H NMR (400 MHz, DMSO-d6) ppm δ 10.48 (s, 1H), 8.07 (d, J=5.1 Hz, 1H), 7.62 (t, J=6.8 Hz, 1H), 7.50-7.55 (m, 3H), 7.34-7.39 (m, 2H), 7.26 (t, J=10.4 Hz, 1H), 6.78 (s, 2H), 6.17 (d, J=5.1 Hz, 1H), 3.25-3.30 (m, 1H), 1.36 (d, J=6.8 Hz, 6H). MS (ESI): 487.8 [M+H]+.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:9]=1[OH:10])[CH:5]=[O:6].[CH3:19][S:20]SC>[Cu].N1C=CC=CC=1>[CH3:19][S:20][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:9]=1[OH:10])[CH:5]=[O:6]
Reactant: O=Cc1cc(Br)c(O)c(OCc2ccccc2)c1
Reactant: CSSC
Agent: [Cu]
Solvent: c1ccncc1
Product: CSc1cc(C=O)cc(OCc2ccccc2)c1O
Temperature: 95 °C
Yield: 75.6 %

Procedure:
In an alternative procedure a 50-L flask equipped with a mechanical stirrer was charged with 3-bromo-4-hydroxy-5-benzyloxybenzaldehyde (1.332 kg, 4.34 mol), Copper powder (1.068 kg, 16.82 mol), dimethyldisulfide (1.068 kg, 11.36 mol) and pyridine (23 L). The mixture was heated at 95° C. overnight with gentle stirring, filtered, and the filtered cake was washed with dichloromethane (30 L). The pyridine filtrate was distilled off to leave a black residue, from which the product was extracted with the dichloromethane washes. The combined organic extracts were washed with 2N HCl until it became light brown and the acidic aqueous layer was clear. The organic layer was dried (MgSO4), filtered, and the filtrate was evaporated to dryness. Crystallization from dichloromethane-hexane gave the title compound (900 g, 76%): mp 117°-119° C.; NMR (CDCl3) δ 2.50 (s, SCH3), 5.20 (s, OCH2Ar), 6.72 (s, OH), 7.34-7.46 (m, ArH), 9.78 (s, ArCHO)