Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[C:7]([CH2:8][CH2:9][CH3:10])=[C:6]([OH:11])[CH:5]=[CH:4][C:3]=1[C:12](=[O:14])[CH3:13].Br[CH2:16][CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:22]([O:21][C:19](=[O:20])[CH2:18][CH2:17][CH2:16][O:11][C:6]1[CH:5]=[CH:4][C:3]([C:12](=[O:14])[CH3:13])=[C:2]([OH:1])[C:7]=1[CH2:8][CH2:9][CH3:10])[CH3:23]
Reactant: CCOC(=O)CCCBr
Reactant: CCCc1c(O)ccc(C(C)=O)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCc1c(OCCCC(=O)OCC)ccc(C(C)=O)c1O
Yield: 55.4 %

Procedure:
A mixture of 2.91 g of 1-(2,4-dihydroxy-3-propylphenyl) ethanone, 2.91 g of ethyl 4-bromobutyrate and 3.1 g of anhydrous potassium carbonate in 35 ml of anhydrous dimethyl formamide was stirred and heated at 75° for 12 hours. The solvent was removed in vacuo, the residue was treated with water and the product was extracted with ethyl acetate. The dried (over magnesium sulfate) extract was concentrated in vacuo and the crude product was purified by chromatography on 200 g of silica gel. Elution with 5% ethyl acetate-toluene gave 2.55 g (54% yield) of 4-(4-acetyl-3-hydroxy-2-propylphenoxy) butanoic acid ethyl ester, the titled compound, as an oil.
Reaction SMILES: [CH:1]1([C:7]([OH:18])([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8]([O:10][CH3:11])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:19]([N:21]([CH2:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=1)[CH2:22][C:23]#[C:24]CO)[CH3:20].C[O-].[Na+]>C1(C)C=CC=CC=1>[CH:12]1([C:7]([OH:18])([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:8]([O:10][CH2:11][C:24]#[C:23][CH2:22][N:21]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[CH2:19][CH3:20])=[O:9])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]1
Reactant: CCN(CC#CCO)Cc1ccc(OC)cc1
Reactant: COC(=O)C(O)(c1ccccc1)C1CCCCC1
Agent: C[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CCN(CC#CCOC(=O)C(O)(c1ccccc1)C1CCCCC1)Cc1ccc(OC)cc1

Procedure:
reacting methyl α-cyclohexyl-α-hydroxybenzeneacetate with said 4-[N-ethyl-(4-methoxyphenyl)methylamino]-2-butyn-1-ol in the presence of sodium methoxide in toluene to produce 4-[N-ethyl-(4-methoxyphenyl)methylamino]-2-butynyl α-cyclohexyl-α-hydroxybenzeneacetate; and
Reaction SMILES: [CH2:1]=[C:2]1[C:7](=[O:8])[CH:6]2[CH2:9][CH2:10][N:3]1[CH2:4][CH2:5]2.C1COCC1>CO.CCOCC.[Pd]>[CH3:1][CH:2]1[C:7](=[O:8])[CH:6]2[CH2:9][CH2:10][N:3]1[CH2:4][CH2:5]2
Reactant: C=C1C(=O)C2CCN1CC2
Agent: [Pd]
Solvent: CCOCC
Solvent: C1CCOC1
Solvent: CO
Product: CC1C(=O)C2CCN1CC2
Reaction time: 0.75 h
Yield: 89.5 %

Procedure:
2-Methylenequinuclidin-3-one (17.8 g, 0.13 mol, 1 eq) is dissolved in 40 mL MeOH in a Parr hydrogenation bottle. A THF slurry of 10% Pd/C (0.57 g) is added. The mixture is hydrogenated for 45 min at 45 psi, recharging as needed. The mixture is filtered through a pad of Celite. The Celite is washed with excess MeOH. The solution is concentrated to give a solid and a yellow oil. The mixture is taken up in ether, filtered and concentrated to provide 16.2 g (90%) of 2-methylquinuclidin-3-one. MS (ESI) for C8H13NO m/z 140.2 (M+).
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH:16]=[CH:15][C:14]([O:17][CH:18]3[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]3)=[CH:13][C:12]2=[O:31])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[ClH:32]>CO>[ClH:32].[CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH:16]=[CH:15][C:14]([O:17][CH:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)=[CH:13][C:12]2=[O:31])=[CH:7][CH:6]=1)(=[O:3])=[O:4]
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2ccn(-c3ccc(S(C)(=O)=O)cc3)c(=O)c2)CC1
Agent: Cl
Solvent: CO
Product: CS(=O)(=O)c1ccc(-n2ccc(OC3CCNCC3)cc2=O)cc1
Reaction time: 1 h

Procedure:
A mixture of tert-butyl 4-(1-(4-(methylsulfonyl)phenyl)-2-oxo-1,2-dihydropyridin-4-yloxy)piperidine-1-carboxylate (2.515 g, 5.61 mmol) and hydrogen chloride (4.0 M in dioxane, 35.0 mL, Aldrich) in methanol (45 mL) was stirred for 1 h and then concentrated in vacuo. The obtained solid was dissolved in methanol and evaporated to give 2.28 g of the crude product as a dark yellow solid. MS (ESI) 349 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([N+:13]([O-])=O)[CH:8]=1)=[O:5].O.O.Cl[Sn]Cl.Cl.[OH-].[NH4+]>C(O)C>[NH2:13][C:9]1[CH:8]=[C:7]([NH:6][C:4](=[O:5])[C:3]2[CH:16]=[CH:17][C:18]([F:20])=[CH:19][C:2]=2[Cl:1])[CH:12]=[CH:11][CH:10]=1
Reactant: O=C(Nc1cccc([N+](=O)[O-])c1)c1ccc(F)cc1Cl
Agent: Cl
Agent: Cl[Sn]Cl
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: Nc1cccc(NC(=O)c2ccc(F)cc2Cl)c1
Yield: 68.8 %

Procedure:
Combine 3-nitroaniline (3.0 g, 21.7 mmol), dichloromethane (100 mL), pyridine (2.11 mL, 26.0 mmol) and 2-chloro-4-fluorobenzoyl chloride (3.07 mL, 23.9 mmol). Stir at room temperature overnight. Filter the white precipitate, rinse with ether (2×10 mL), and dry under vacuum to provide 2-chloro-4-fluoro-N-(3-nitrophenyl)benzamide (4.92 g, 77%). Combine the 2-chloro-4-fluoro-N-(3-nitrophenyl)benzamide (4.92 g, 16.7 mmol) with ethanol (150 mL), SnCl2.2H2O (18.9 g, 83.6 mmol) and concentrated hydrochloric acid (8.24 mL, 83.6 mmol). Stir at reflux under a nitrogen atmosphere for 2 hr. Neutralize with ammonium hydroxide (15 mL). Filter through celite, wash with dichloromethane (2×15 mL), separate the filtrate, extract with dichloromethane (2×80 mL), and dry the combined organic layers over magnesium sulfate. Filter and concentrate to dryness to provide the title intermediate as an off-white solid (3.04 g, 69%): mass spectrum (ion spray): m/z=265.0(M+1); 1H NMR (DMSO-d6): 10.16 (bs, N—H), 7.60 (dd, J=6.2 Hz, 8.6 Hz, 1H), 7.54 (dd, J=2.5 Hz, 9.0 Hz, 1H), 7.30 (td, J=2.5 Hz, 8.5 Hz, 1H), 7.04 (t, J=2.0 Hz, 1H), 6.93 (t, J=8.0 Hz, 1H), 6.74 (bd, J=7.9 Hz, 1H), 6.29 (dd, J=2.2 Hz, 7.9 Hz, 1H), 5.10 (bs, 2H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=O.O=S(Cl)[Cl:14]>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([Cl:14])=[O:11]
Reactant: O=C(O)Cc1ccccc1F
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: O=C(Cl)Cc1ccccc1F

Procedure:
To a solution of 2-fluorophenylacetic acid (450 g, 3.0 mol) in CH2Cl2 (900 mL) is added SOCl2 (714 g, 6 mol) dropwise. After addition is complete, the reaction mixture is heated to reflux for 2 hours. Subsequently, the solvent is removed in vacuo after which vacuum distillation of the resulting oil provides 2-fluorobenzeneacetyl chloride.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[N:4]=[C:5]([C:31]2[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=2)[N:6]([C@@H:8]([C:12]2[O:13][C:14]3[C:19]([C:20](=[O:29])[C:21]=2[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:18][CH:17]=[C:16]([Cl:30])[CH:15]=3)[CH:9]([CH3:11])[CH3:10])[CH:7]=1.N1C=CC=CC=1.[CH3:44][C:45](OC(C)=O)=[O:46]>>[CH2:22]([CH:21]1[C:20](=[O:29])[C:19]2[C:14](=[CH:15][C:16]([Cl:30])=[CH:17][CH:18]=2)[O:13][CH:12]1[C@H:8]([N:6]1[CH:7]=[C:3]([CH2:2][NH:1][C:45](=[O:46])[CH3:44])[N:4]=[C:5]1[C:31]1[CH:36]=[CH:35][C:34]([CH3:37])=[CH:33][CH:32]=1)[CH:9]([CH3:11])[CH3:10])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: Cc1ccc(-c2nc(CN)cn2[C@@H](c2oc3cc(Cl)ccc3c(=O)c2Cc2ccccc2)C(C)C)cc1
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)NCc1cn([C@H](C(C)C)C2Oc3cc(Cl)ccc3C(=O)C2Cc2ccccc2)c(-c2ccc(C)cc2)n1
Yield: 88.8 %

Procedure:
To 2-[(R)-1-(4-aminomethyl-2-p-tolyl-imidazol-1-yl)-2-methyl-propyl]-3-benzyl-7-chloro-chromen-4-one (0.17 g, 0.33 mMol) in CH2Cl (5 mL) was added with stirring, pyridine (27 uL, 0.33 mMol) and Ac2O (63 uL, 0.67 mMol). After stirring at RT for 4 h the reaction was concentrated under vacuum. The remaining residue was triturated with (1:1) Et2O/pet. ether, filtered and dried under vacuum to give the title compound (163 mg, 89%) as a white solid: 1H NMR (400 MHz, CDCl3) δ 8.14 (d, J=8.6 Hz, 1H), 7.59 (d, J=1.8 Hz, 1H), 7.43 (m, 6H), 7.17 (m, 3H), 6.84 (br s, 1H), 6.71 (d, J=2.2 Hz, 1H), 6.69 (s, 1H), 5.07 (d, J=10.9 Hz, 1H), 4.50 (2d, 1H), 4.43 (2d, 1H), 4.07 (d, J=15.5 Hz 1H), 2.66 (m, 1H), 2.51 (s, 3H), 2.48 (d, J=15.5 Hz, 1H), 2.00 (s, 3H), 0.95 (d, 6.6 Hz, 3H), 0.34 (d, J=6.7 Hz, 3H); MS (ES) m/e 554.4 (M+14)+.
Reaction SMILES: COC(=O)C.C[O:7][C:8](=O)[CH2:9][O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]([C:21](=[O:29])[C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=1)[C@@H:16]([CH3:30])[CH2:15][C@H:14]2[N:31]([C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=1)[C:32](=[O:35])[CH2:33][CH3:34].[NH3:44]>CO>[C:8]([CH2:9][O:10][C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[N:17]([C:21](=[O:29])[C:22]1[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=1)[C@@H:16]([CH3:30])[CH2:15][C@H:14]2[N:31]([C:36]1[CH:37]=[CH:38][C:39]([Cl:42])=[CH:40][CH:41]=1)[C:32](=[O:35])[CH2:33][CH3:34])(=[O:7])[NH2:44]
Reactant: N
Reactant: CCC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(F)cc2)c2ccc(OCC(=O)OC)cc21
Solvent: COC(C)=O
Solvent: CO
Product: CCC(=O)N(c1ccc(Cl)cc1)[C@@H]1C[C@H](C)N(C(=O)c2ccc(F)cc2)c2ccc(OCC(N)=O)cc21
Temperature: 25 °C

Procedure:
(±)-Cis-N-[6-carbamoylmethoxy-1-(4-fluoro-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-4-yl]-N-(4-chloro-phenyl)-propionamide was prepared from (±)-cis-4-[(4-chloro-phenyl)-propionyl-amino]-1-(4-fluoro-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-6-yloxy]-acetic acid methyl ester. To solid (±)-cis-[4-[(4-chloro-phenyl)-propionyl-amino]-1-(4-fluoro-benzoyl)-2-methyl-1,2,3,4-tetrahydro-quinolin-6-yloxy]-acetic acid methyl ester (76 mg, 0.14 mmol) was added a solution of ammonia in methanol (2 M, 10 mL). The resulting solution was stirred over night at room temperature and concentrated. The resulting crude amide was purified by silica gel chromatography (100% hexanes—100% ethyl acetate gradient) to afford pure product (59 mg, 76%).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=1.[Cl:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1B(O)O.O>COCCOC.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=1
Reactant: OB(O)c1ccccc1Cl
Reactant: FC(F)(F)c1ccnc(Cl)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: O
Solvent: COCCOC
Product: FC(F)(F)c1ccnc(-c2ccccc2Cl)c1
Temperature: 110 °C
Yield: 89.1 %

Procedure:
A mixture of 2-chloro-4-(trifluoromethyl)pyridine (4 g, 22.0 mmol), 2-chlorophenylboronic acid (5.04 g, 24.2 mmol), Ba(OH)2 (12.5 g, 66.1 mmol) and Pd(PPh3)2Cl2 (464 mg, 0.66 mmol) in DME (140 mL)/water (35 mL) was heated at 110° C. for 1 h. The solids were filtered off and the mother liquor were concentrated to around 80 mL and extracted with EtOAc. The organic layer was washed with brine, then water, dried (MgSO4), filtered and concentrated. Purification by column chromatography (1/1 Petroleum ether/EtOAc) gave the Suzuki adduct (5.05 g, 89%) as a colourless oil.
Reaction SMILES: O=O.[CH3:3][C:4]([CH3:16])=[C:5]([C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=1)[C:6]([OH:8])=[O:7].C(N(CC)CC)C>O>[F:15][C:12]1[CH:11]=[CH:10][C:9]([C@@H:5]([CH:4]([CH3:16])[CH3:3])[C:6]([OH:8])=[O:7])=[CH:14][CH:13]=1
Reactant: CC(C)=C(C(=O)O)c1ccc(F)cc1
Agent: O=O
Solvent: CCN(CC)CC
Solvent: O
Product: CC(C)[C@@H](C(=O)O)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 95.2 %

Procedure:
In a glove box (argon-atmosphere, O2 -content<1 ppm) a 10 ml measuring flask was charged with 16.9 mg (0.013 mmol) of ((S)-MeOBIPHEP-TS-Na)Ru(OCOF3)2 and filled to the graduation mark with 10 ml of degassed water. The suspension was stirred with a magnetic stirring bar for 15 min at room temperature A clear yellow solution formed. In the glove box a 30 ml stainless steel autoclave fitted with a magnetic stirring bar was charged with 0.5 g (2.57 mmol) of 3-methyl-2-(p-fluorophenyl)crotonic acid, 7.5 ml of degassed water and 0.26 g (2.57 mmol) of degassed triethylamine. To this suspension 2.0 ml of the above catalyst solution was added and the autoclave was then sealed, pressurized with 6 bar of argon and removed from the glove box. The autoclave was connected to a hydrogenation line, which was thoroughly flushed with hydrogen. The argon in the autoclave was replaced by 60 bar of hydrogen and the hydrogenation was carried out by stirring at 20° and 60 bar. After a reaction time of 21 h the autoclave was vented. The light yellow reaction mixture was transferred to a 50 ml separatory funnel, acidified at 20-25° by adding 2.7 ml of 1N aqueous hydrochloric acid and extracted with ether. The combined ether extracts were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and concentrated to dryness by rotary evaporation. Distillation of the reddish residue at 160° and 0.1 mbar afforded 0.48 g of (R)-2-(4-fluorophenyl)-3-methylbutyric acid as a colorless oil, which solidified on standing at room temperature; ee 84% (determined by GC on a chiral permethylated β-cyclodextrin column); purity>99 GC-area %.
Reaction SMILES: [Li]CCCC.C[N:7]([CH3:12])[CH2:8][CH2:9]NC.N1C=[CH:17][CH:16]=[C:15]([CH:19]=[O:20])C=1.IC.[Na+].[Cl-]>C1COCC1>[CH3:17][C:16]1[CH:9]=[CH:8][N:7]=[CH:12][C:15]=1[CH:19]=[O:20]
Reactant: CNCCN(C)C
Reactant: O=Cc1cccnc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CI
Product: Cc1ccncc1C=O
Reaction time: 0.25 h

Procedure:
n-BuLi (1.6M in hexanes) (2.2 mmol, 1.37 ml) was added dropwise to a stirred solution of N,N,N'-trimethylethylenediamine (2.4 mmol, 0.245 g) in THF at -78° C. A solution of 3-pyridinecarboxaldehyde (2 mmol, 0.214 g) in THF was added and the mixture stirred for 15 min before adding a further portion of n-BuLi (1.6M in hexanes) (4 mmol, 2.5 ml). After stirring for 2 h at -70° C., iodomethane was added, the mixture stirred at RT for 30 min, then poured into aqueous NaCl solution, extracted twice with Et2O, dried (MgSO4), filtered and concentrated in vacuo. The residue was subjected to chromatography (SiO2 ; Et2O) to afford the title compound as an oil.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13](Br)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][C:24]=1[F:25].ClCCl.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:21]3[CH:22]=[CH:23][C:24]([F:25])=[C:19]([Cl:18])[CH:20]=3)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OB(O)c1ccc(F)c(Cl)c1
Reactant: Brc1ccc2c(ccn2Cc2ccccc2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: ClCCl
Solvent: C1COCCO1
Product: Fc1ccc(-c2ccc3c(ccn3Cc3ccccc3)c2)cc1Cl
Yield: 41.2 %

Procedure:
1-Benzyl-5-(3-chloro-4-fluorophenyl)-1H-indole was prepared by coupling 1-benzyl-5-bromo-1H-indole (1.46 g, 5.10 mmol), and 3-chloro-4-fluorophenylboronic acid (1.08 g, 6.19 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (0.209 g, 0.256 mmol), potassium carbonate (1.44 g, 10.4 mmol) in dioxane (51 mL) and water (5 mL), following the procedure described in Step 1 of Example 11. Purification by flash chromatography (Biotage apparatus) using hexane as an eluant and drying 60° C. furnished the title compound as a light brown gum (0.706 g, 41%). 1HNMR (200 MHz, DMSO-d6): δ 7.8-7.9 (m, 2H), 7.6-7.7 (m, 1H), 7.4-7.6 (m, 3H), 7.15-7.4 (m, 6H), 6.55 (d, 1H, J=2.5 Hz), and 5.45 ppm (s, 2H).
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:14]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@@H:13]([CH2:32][O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:12][CH:10]1[OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[K+].Br[CH2:44][CH2:45][CH2:46][N:47]1C(=O)C2=CC=CC=C2C1=O.O.NN>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C(OCOCC)C.COCCOC.C1C=CC=CC=1>[CH2:1]([O:8][C@@H:9]1[C@@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:14]([O:24][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C@@H:13]([CH2:32][O:33][CH2:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[O:12][CH:10]1[O:11][CH2:44][CH2:45][CH2:46][NH2:47])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C1c2ccccc2C(=O)N1CCCBr
Reactant: OC1O[C@H](COCc2ccccc2)[C@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: NN
Agent: O=S(=O)([O-])O
Solvent: c1ccccc1
Solvent: COCCOC
Solvent: O
Product: NCCCOC1O[C@H](COCc2ccccc2)[C@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Temperature: 10 °C

Procedure:
A mixture that consists of 42.1 g (100 mmol) of 2,3,4,6-tetra-O-benzyl-galactopyranose, 1.7 g (5 mmol) of tetrabutylammonium hydrogen sulfate and 33.7 g (600 mmol) of fine-powder potassium hydroxide in 350 ml of diethoxymethane is cooled to 10° C. At 10° C., 40.2 g (150 mmol) of N-(3-bromopropyl)-phthalimide, dissolved in 100 ml of 1,2-dimethoxyethane, is added in drops over 40 minutes while being stirred vigorously. It is stirred for three hours at 10° C. 300 ml of benzene is added, solid is filtered out, and the filtrate is evaporated to the dry state in a vacuum. The filtrate residue is dissolved in 500 ml of ethanol, 25.03 ml of hydrazine hydrate (500 mmol) is added, and it is refluxed for six hours. It is allowed to cool to 0° C., deposited precipitate is filtered out, and the filtrate is evaporated to the dry state in a vacuum. The residue is dissolved in 400 ml of dichloromethane, this solution is washed twice with 5% aqueous sodium hydroxide solution, then once with water (in each case 300 ml). The organic phase is evaporated to the dry state in a vacuum, and the residue is chromatographed on silica gel (mobile solvent: dichloromethane/ethanol/triethylamine=20:2:0.1).
Reaction SMILES: [N+]([C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:19])[C:8]=2[CH:7]=[CH:6][CH:5]=1)([O-])=O.[Br:20]Br>ClC1C=CC=CC=1>[Br:20][C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:19])[C:8]=2[CH:7]=[CH:6][CH:5]=1
Reactant: BrBr
Reactant: O=C1c2ccccc2C(=O)c2c1cccc2[N+](=O)[O-]
Solvent: Clc1ccccc1
Product: O=C1c2ccccc2C(=O)c2c(Br)cccc21
Temperature: 240 °C

Procedure:
In an apparatus as described in Example 1, 1265 parts pf 1-nitroanthraquinone are melted by heating to 240° C. and then elemental bromine is pumped in, with efficient stirring, at 245°-250° C. The rate of addition is so chosen that gentle bromine reflux is constantly mantained in the reflux condenser. After about 624 parts of bromine have been added over about 10 hours, no more bromine is taken up by the reaction mixture and the presence of 1-nitroanthraquinone can no longer be detected in a thin-layer chromatogram. The mixture is cooled to 200° C. and the melt is discharged into 1200 parts of efficiently stirred chlorobenzene. The resultant suspension is cooled to 20° C. and filtered. The filter cake is washed with chlorobenzene and the crystals are dried in vacuo at 120° C., affording 1350 parts of 1-bromoanthraquinone in 99-99.5% purity. The yield, based on 1-nitroanthraquinone, is 96%.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[O:9][CH2:10][C:11]([OH:13])=[O:12].[OH-].[K+:15]>CO>[CH3:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[O:9][CH2:10][C:11]([O-:13])=[O:12].[K+:15]
Reactant: Cc1cc(Cl)ccc1OCC(=O)O
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: Cc1cc(Cl)ccc1OCC(=O)[O-]
Yield: 100 %

Procedure:
A melt of 20 parts (0.1 mol) of MCPA (94.7%) is reacted with 100 ml of 1 molar methanolic potassium hydroxide solution (0.1 mol) at 130° C. with removal of methanol by distillation. After complete removal of methanol by distillation, 25.1 parts of MCPA-potassium are obtained, containing 73.3% of MCPA of m.p. 200-205° C., which corresponds to a yield of 100%.
Reaction SMILES: C(NC(C)C)(C)C.[Li]CCCC.CCCCCC.[Li+].CC([N-]C(C)C)C.[F:27][C:28]1[CH:33]=[CH:32][C:31]([Br:34])=[CH:30][CH:29]=1.CC[O:37][C:38]([CH:40]([F:42])[F:41])=O>C1COCC1>[Br:34][C:31]1[CH:30]=[CH:29][C:28]([F:27])=[C:33]([C:38](=[O:37])[CH:40]([F:42])[F:41])[CH:32]=1
Reactant: CCOC(=O)C(F)F
Reactant: Fc1ccc(Br)cc1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: CCCCCC
Solvent: C1CCOC1
Product: O=C(c1cc(Br)ccc1F)C(F)F
Temperature: -40 °C

Procedure:
A solution of diisopropyl amine (17.77 ml, 126 mmol) in 320 ml THF was cooled to −75° C. and brought under N2 atmosphere. A 1.6 M solution of BuLi in hexane (79 ml, 126 mmol) was added. When the LDA solution had cooled down again, 1-fluoro-4-bromobenzene was added. The reaction temperature was kept below −60° C. After 2.5 h ethyl difluoro acetate (15.60 g, 126 mmol) was added rapidly and after 15 minutes, the reaction mixture was warmed to −40° C. After 15 minutes the mixture was quenched by pouring it on ice-cold 1N HCl. The mixture was extracted with petroleum ether (B.p. 40-60° C.) and the extract was dried with MgSO4.H2O. Chromatography on silica gel with hexane/TBME 9/1->6/1 gave 22.1 g yellow liquid.
Reaction SMILES: [N+:1]([C:4]1[CH:8]=[N:7][N:6]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[C:5]=1[C:17](OCC)=[O:18])([O-:3])=[O:2].[BH4-].[Na+].[Cl-].[NH4+].Cl>C(OCC)(=O)C.CO>[N+:1]([C:4]1[CH:8]=[N:7][N:6]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:14])([CH3:15])[CH3:16])[C:5]=1[CH2:17][OH:18])([O-:3])=[O:2]
Reactant: CCOC(=O)c1c([N+](=O)[O-])cnn1COCC[Si](C)(C)C
Agent: Cl
Agent: [BH4-]
Agent: [Cl-]
Solvent: CO
Solvent: CCOC(C)=O
Product: C[Si](C)(C)CCOCn1ncc([N+](=O)[O-])c1CO
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 89.6 %

Procedure:
To a 0° C. solution of 4-nitro-2-(2-trimethylsilanyl-ethoxymethyl)-2H-pyrazole-3-carboxylic acid, ethyl ester (10 g, 31.7 mmol) in tetrahydroftiran (200 mL) was added methanol (24 mL) followed by sodium borohydride (9.59 g, 8 eq) in one portion. The resulting mixture was stirred at 0° C. for 20 minutes. The reaction mixture was then added to a mixture of saturated aqueous ammonium chloride solution (600 mL) and ethyl acetate (800 mL) in an ice-bath. A solution of 4 N HCl was added with stirring at 0° C. to adjust the pH of the aqueous layer to about 4. The organic layer was separated and washed with brine (1×500 mL), dried over magnesium sulfate, filtered and concentrated to give the title compound (7.76 g) as a reddish oil. M+=273.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])[C:5]([O:7]C)=[O:6].[F:16][C:17]([F:22])([F:21])C([O-])=O.[K+].C1(C)C=CC=CC=1.[OH-].[Na+]>CN(C=O)C.CO.[Cu]I.CCOCC>[CH:13]([O:12][C:11]1[CH:10]=[CH:9][C:4]([C:5]([OH:7])=[O:6])=[CH:3][C:2]=1[C:17]([F:22])([F:21])[F:16])([CH3:15])[CH3:14]
Reactant: O=C([O-])C(F)(F)F
Reactant: COC(=O)c1ccc(OC(C)C)c(Br)c1
Agent: [Cu]I
Agent: [K+]
Agent: [Na+]
Solvent: CO
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: CC(C)Oc1ccc(C(=O)O)cc1C(F)(F)F
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Methyl 3-bromo-4-iso-propyloxybenzoate (828 mg; 3.03 mmol) was dissolved in DMF (25 ml) and treated with potassium trifluoroacetate (922 mg; 6.06 mmol), copper (I) iodide (1.15 g; 6.06 mmol) and toluene (50 ml). The resulting mixture was heated at reflux for 1.5 h under Dean and Stark conditions with removal of ca 50 ml of distillate. The resulting mixture was heated at reflux for 18 h then cooled to room temperature, before being poured into a mixture of Et2O (100 ml) and HO (100 ml). The two-phase mixture was stirred at room temperature for 0.5 h then filtered through Celite. The two phases in the filtrate were separated, the aq. phase further extracted with Et2O (50 ml) and the organic extracts combined, washed with saturated, aq. Na2S2O3, H2O, saturated brine, dried (MgSO4) and evaporated to dryness under reduced pressure to give a brown oil. This brown oil was dissolved in MeOH (ca 20 ml) and treated with 2M aq. sodium hydroxide solution (2 ml; 4 mmol) and the resulting solution heated at reflux for 3h. The volatiles were removed under reduced pressure and the residue partitioned between EtOAc and H2O. The phases were separated, the aq. phase acidified to pH1 with 2M hydrochloric acid in the presence of EtOAc and the phases separated. The aq. phase was further extracted with EtOAc, the extracts combined, washed with H2O, saturated brine, dried (MgSO4) and evaporated to dryness underreduced pressure to give the title compound as a white solid. (671 mg; 89%).