Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=2)=[CH:10][CH:9]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].C1(C)C=CC=CC=1.CO>C(O)C.[Ni]>[CH2:1]([C:8]1[CH:9]=[CH:10][C:11]([C@H:14]2[CH2:19][CH2:18][C@H:17]([OH:20])[CH2:16][CH2:15]2)=[CH:12][CH:13]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: CCCCCCCc1ccc(-c2ccc(O)cc2)cc1
Agent: [Ni]
Solvent: CCO
Solvent: Cc1ccccc1
Solvent: CO
Product: CCCCCCCc1ccc([C@H]2CC[C@H](O)CC2)cc1
Temperature: 110 °C
Reaction time: 1 h

Procedure:
4-(4'-Heptylphenyl)phenol (200 g) was dissolved in ethanol (0.5 l) and a commercially available Raney nickel catalyst (20 g) was added, followed by hydrogenation at 80°~120° C. under hydrogen pressures of 30~40 Kg/cm2G for 6 hours in an autoclave. The reaction was traced by gas chromatography (column: SIDC-560-10%, 2 m, 280° C.), and when the raw material was extinct, the reaction was stopped. The catalyst was filtered off from the hydrogenation product, and after ethanol was distilled off under reduced pressure, the product was dissolved in toluene (200 ml). On the other hand, metallic sodium (18.4 g) was added to toluene (400 ml), followed by heating to 110° C. and then quenching down to room temperature under high speed agitation to prepare a sodium dispersion. To this dispersion was added the above toluene solution of the hydrogenation product, followed by stirring at room temperature for one hour. The mixture was further agitated at 100° C. for 4 hours, followed by cooling and then gradually adding methanol (200 ml). The whole mixture was transferred into a separating funnel and washed twice with 10% hydrochloric acid (200 ml) and once with a saturated aqueous solution of sodium hydrogen carbonate (200 ml), followed by repeated washings with water until the water layer became neutral. The toluene layer was dried over anhydrous sodium sulfate and toluene was distilled off under reduced pressure, followed by adding n-hexane (200 ml) and standing still overnight obtain crystals of trans-4-(4'-heptylphenyl)cyclohexanol. Yield: 41.6 g, 20.4%, m.p.: 80.2°~82.5° C.
Reaction SMILES: [NH2:1][C:2]1[C:3]([CH3:11])=[C:4]([C:8]([OH:10])=[O:9])[CH:5]=[N:6][CH:7]=1.S(Cl)(Cl)=O.[CH3:16]O>>[NH2:1][C:2]1[C:3]([CH3:11])=[C:4]([C:8]([O:10][CH3:16])=[O:9])[CH:5]=[N:6][CH:7]=1
Reactant: Cc1c(N)cncc1C(=O)O
Reactant: CO
Solvent: O=S(Cl)Cl
Product: COC(=O)c1cncc(N)c1C
Temperature: 50 °C
Reaction time: 64 h
Yield: 80 %

Procedure:
To a stirred solution of 5-amino-4-methylpyridine-3-carboxylic acid (0.94 g, 6.18 mmol) in MeOH (20 ml at 0° C. was added thionyl chloride drop-wise. The solution was then heated to 50° C. for 3.5 h, a further 10 ml of MeOH was added and the reaction heated at 50° C. for 5 h followed by stirring at room temperature for 64 h. The solvent was then evaporated under reduced pressure and saturated NaHCO3 solution was added until pH7-8. The product was extracted into EtOAc (2×50 ml) and the combined organics were washed with brine (50 ml) dried using Na2SO4, filtered and evaporated to afford the title compound as an off-white powder (824 mg, 80%) which was suitable for use in the next stage without any purification. LC-MS m/z=167.0, 1H NMR (500 MHz, Chloroform-d) δ 8.52 (d, J=34.2 Hz, 1H), 8.16 (s, 1H), 3.95 (d, J=4.8 Hz, 3H), 3.78 (s, 2H), 2.42 (s, 3H).
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][CH2:6]2>Br.CC(O)=O>[OH:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][CH2:6]2
Reactant: COc1ccc2c(c1)CCC2=O
Agent: Br
Solvent: CC(=O)O
Product: O=C1CCc2cc(O)ccc21
Temperature: 23 °C
Yield: 36 %

Procedure:
A solution of 5-methoxy-indan-1-one (4.9 grams, 30 mmol)in 1:1 concentrated HBr/HOAc (150 mL) was heated at 112° C. for 28 hours. The reaction was cooled to 23° C. and filtered through celite. The filtrate was diluted with ethyl acetate (1000 mL) and washed with saturated aqueous NaCl (100 mL), saturated aqueous NaHCO3 (2×100 mL) and with saturated aqueous NaCl (100 mL). The ethyl acetate solution was dried (MgSO4) and concentrated in vacuo to give 1.6 grams of crude product. 1H NMR (250 MHz, d6 -DMSO): d 7.45 (d, 1 H), 6.82 (s, 1 H), 6.78 (d, 1 H), 2.95 (t, 2H), 2.55 (t, 2 H).
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][CH2:6]2.[Na].C(C1C=CC(S)=C(C)C=1)(C)(C)C.O.Cl>CCOC(C)=O>[OH:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[CH2:7][CH2:6]2
Reactant: COc1ccc2c(c1)CCC2=O
Agent: Cc1cc(C(C)(C)C)ccc1S
Agent: Cl
Agent: [Na]
Solvent: CCOC(C)=O
Solvent: O
Product: O=C1CCc2cc(O)ccc21
Temperature: 25 °C
Yield: 45.8 %

Procedure:
5-Methoxy-indan-1-one (8 g, 49.3 mmol), and 4-tert-butyl-2-methyl-benzenethiol sodium salt (11.92 g, 59.2 mmol) were heated at 142° C. for 1 hr under argon. After cooling to RT, water (80 ml) was added followed by 1N HCl (80 ml) and EtOAc (120 ml). The mixture was shaken and the aqueous phase extracted with EtOAc (100 ml), the combined organic extracts were washed with satd.NaCl solution (100 ml) and dried with Na2SO4, filtered and evaporated. The residue was chomatographed over SiO2 (Merck 230-400 mesh) eluting with EtOAc-nHexane (2:3), producing 5-hydroxy-indan-1-one (3.55g, 22.6 mmol, 45.9 %) as orange crystals Mp. 185-187° C., MS m/e=148.2 (M+).
Reaction SMILES: C([O:3][C:4]([C:6]1[S:7][CH:8]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:10]=1)=[O:5])C.[OH-].[K+]>CO>[C:11]1([C:9]2[N:10]=[C:6]([C:4]([OH:5])=[O:3])[S:7][CH:8]=2)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: CCOC(=O)c1nc(-c2ccccc2)cs1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)c1nc(-c2ccccc2)cs1
Yield: 76.5 %

Procedure:
To a solution of 4-phenyl-thiazole-2-carboxylic acid ethyl ester (282 mg, 1.21 mmol) dissolved in methanol (10 ml) was added 1N—KOH (3.63 ml, 3.63 mmol) and the mixture was allowed to react at 60° C. for 15 minutes. After the solvent was evaporated from the reaction mixture, the residue was dissolved by adding water and acidified (pH=2) with 2N—HCl under ice cooling. The produced precipitates were filtered with suction, washed with water and recrystallized from methanol-water to afford 190 mg (yield 72%) of the desired 4-phenyl-thiazole-2carboxylic acid as white solids.
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]1([CH3:16])[C:8]([CH3:10])([CH3:9])[O:7][B:6]([C:11]2[CH:12]=[N:13][NH:14][CH:15]=2)[O:5]1.[CH3:17][C:18]1([CH3:21])[CH2:20][O:19]1>CN(C=O)C>[CH3:17][C:18]([OH:19])([CH3:21])[CH2:20][N:14]1[CH:15]=[C:11]([B:6]2[O:7][C:8]([CH3:9])([CH3:10])[C:4]([CH3:16])([CH3:3])[O:5]2)[CH:12]=[N:13]1
Reactant: CC1(C)CO1
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(O)Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Temperature: 100 °C

Procedure:
Sodium hydride (58.74 mg, 0.002448 mol) was added to solution of 4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (500.0 mg, 0.002577 mol) in DMF (5 mL) at room temperature. After gas evolution ceased, 2,2-dimethyl-oxirane, (0.46 mL, 0.0052 mol) was added. The mixture was heated to 100° C. for 1 hour. The material was extracted with EtOAc, and washed with water (3×). The organic layer was concentrated in vacuo to afford the title compound as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ=1.04 (s, 6 H), 1.25 (s, 12 H), 4.03 (s, 2 H), 4.68 (s, 1 H), 7.56 (s, 1 H), 7.84 (s, 1 H).
Reaction SMILES: [C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[CH:12](OCC)(OCC)[O:13][CH2:14][CH3:15].C(OC(=O)C)(=O)C>OP(O)(O)=O>[CH2:14]([O:13][CH:12]=[C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][CH2:10][CH3:11])=[O:8])[CH3:15]
Reactant: CCOC(OCC)OCC
Reactant: CCOC(=O)CC(=O)OCC
Agent: O=P(O)(O)O
Solvent: CC(=O)OC(C)=O
Product: CCOC=C(C(=O)OCC)C(=O)OCC
Yield: 92.5 %

Procedure:
160.2 g (1.0 mol) of diethyl malonate, 474.2 g (3.2 mol) of triethyl orthoformate and 0.5 g of catalyst from Example 5 were initially introduced and the mixture was heated to boiling. A mixture of 10 g of acetic anhydride, 1 g of H3PO4 and 30 g of triethyl orthoformate were continuously added dropwise over the course of 6 hours. The reaction and work up were carried out in accordance with Example 3 and gave 200 g of diethyl ethoxymethylenemalonate, which corresponds to a yield of 92.6% of the theoretical yield.
Reaction SMILES: C([N:8]1[C:13](=[O:14])[C:12]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)=[C:11]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)[C:10]([O:29]CC2C=CC=CC=2)=[N:9]1)C1C=CC=CC=1.C1(C)C=CC=CC=1.[Cl-].[Al+3].[Cl-].[Cl-]>O>[Cl:28][C:25]1[CH:24]=[CH:23][C:22]([C:11]2[C:10](=[O:29])[NH:9][NH:8][C:13](=[O:14])[C:12]=2[C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)=[CH:27][CH:26]=1
Reactant: O=c1c(-c2ccc(Cl)cc2)c(-c2ccc(Cl)cc2)c(OCc2ccccc2)nn1Cc1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: Cc1ccccc1
Solvent: O
Product: O=c1[nH][nH]c(=O)c(-c2ccc(Cl)cc2)c1-c1ccc(Cl)cc1
Temperature: 90 °C
Reaction time: 2 h

Procedure:
To a round bottom flask was added 2-benzyl-6-(benzyloxy)-4,5-bis(4-chlorophenyl)pyridazin-3(2H)-one (15.5 gm, 30.21 mmol), toluene (70 ml) and aluminum chloride (10.08 gm, 75.54 mmol). The reaction was stirred at 90° C. for 2 h. After this time, the reaction was cooled to 0° C. and water (200 ml) was slowly added to the reaction. The solution was extracted with ethyl acetate (3 L). The organic layer was washed with water (200 ml) and saturated aqueous NaCl (200 ml). The organic layer was dried (MgSO4), filtered and concentrated. The title compound, 4,5-bis(4-chlorophenyl)-1,2-dihydropyridazine-3,6-dione, was obtained as a solid and used in next reaction without further purification. MS (M+H)=330.9, 333.0.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH2:14][OH:15])[CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1)([O-])=O.Cl.O.O.Cl[Sn]Cl.C([O-])(O)=O.[Na+]>C1COCC1>[NH2:1][C:4]1[CH:5]=[C:6]([CH2:14][OH:15])[CH:7]=[C:8]([C:10]([F:11])([F:12])[F:13])[CH:9]=1
Reactant: O=[N+]([O-])c1cc(CO)cc(C(F)(F)F)c1
Agent: Cl
Agent: Cl[Sn]Cl
Agent: O=C([O-])O
Solvent: O
Solvent: C1CCOC1
Product: Nc1cc(CO)cc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 24 h
Yield: 98.1 %

Procedure:
To a solution of [3-nitro-5-(trifluoromethyl)phenyl]methanol (1.8 g, 8.0 mmol) (Step A, Example 23) in THF (36 mL) was added concentrated HCl (18 mL) and SnCl2.2H2O (8.7 g, 38.8 mmol). The reaction was stirred at room temperature for 24 hours and then poured slowly into saturated NaHCO3 (250 mL). After neutralization was complete, the reaction was extracted with EtOAc (3×50 mL). The organic extracts were washed with brine (75 mL), dried over Na2SO4, filtered, and concentrated. Purification by flash chromatography with 50% EtOAc/hexanes afforded 1.5 g (quantitative) of [3-amino-5-(trifluoromethyl)phenyl]methanol. Rf=0.35 (50% EtOAc/hexanes). 1H NMR (CDCl3, 500 MHz) δ 6.98 (s, 1H), 6.84 (s, 1H), 6.81 (s, 1H), 4.65 (s, 2H), 3.87 (bs, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.[NH2:41][C:42]1[CH:43]=[C:44]([CH:47]=[CH:48][CH:49]=1)[C:45]#[N:46]>CN(C=O)C.O>[C:45]([C:44]1[CH:43]=[C:42]([NH:41][C:7](=[O:9])[C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:11][CH:10]=2)[CH:49]=[CH:48][CH:47]=1)#[N:46]
Reactant: COc1ccc(C(=O)O)cc1
Reactant: N#Cc1cccc(N)c1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN1CCOCC1
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(C(=O)Nc2cccc(C#N)c2)cc1
Reaction time: 0.25 h

Procedure:
5.0 g (33 mmol) 4-methoxybenzoic acid were dissolved in 50 ml DMF. 12.8 g (66 mmol) EDCl, 9.2 g (66 mmol) HOBt and 14.8 ml (132 mmol) 4-methylmorpholine were added and the mixture was stirred for 15 min. Subsequently, 3.9 g (33 mmol) 3-aminobenzonitrile were added and the mixture was stirred for 48 h at room temperature and 6 h at 80° C. The reaction mixture was poured in 500 ml water and the precipitate was filtered, washed and dried.
Reaction SMILES: [NH:1]1[CH2:9][CH2:8][CH:4]([C:5]([OH:7])=[O:6])[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].[C:16](Cl)(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.Cl>O>[C:16]([N:1]1[CH2:9][CH2:8][CH:4]([C:5]([OH:7])=[O:6])[CH2:3][CH2:2]1)(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: O=C(O)C1CCNCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: O=C(O)C1CCN(C(=O)c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 95 %

Procedure:
To an ice cold solution of isonipecotic acid (90 g, 0.697 mol) and potassium carbonate (81 g, 1.31 mol) in water (1.3 liter) was added dropwise benzoyl chloride (81 ml, 0.697 mol) over a period of about an hour at about 5° C. The mixture was stirred at room temperature overnight. The reaction mixture was acidified with 6N hydrochloric acid and extracted with dichloromethane. The organic layer was washed with water and then dried over magnesium sulfate and the solvent was evaporated in vacuo. Crystallization from isopropyl alcohol-diethyl ether to give the titled compound (154.4 g).
Reaction SMILES: [N:1]1([C:7]2[N:8]=[C:9]([CH2:14][C:15]([O-:17])=O)[NH:10][C:11](=[O:13])[CH:12]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Na+].[NH2:19][C:20]1[CH:21]=[C:22]([CH:27]=[CH:28][CH:29]=1)[O:23][CH2:24][CH2:25][OH:26]>>[OH:26][CH2:25][CH2:24][O:23][C:22]1[CH:21]=[C:20]([NH:19][C:15](=[O:17])[CH2:14][C:9]2[NH:10][C:11](=[O:13])[CH:12]=[C:7]([N:1]3[CH2:2][CH2:3][O:4][CH2:5][CH2:6]3)[N:8]=2)[CH:29]=[CH:28][CH:27]=1
Reactant: O=C([O-])Cc1nc(N2CCOCC2)cc(=O)[nH]1
Reactant: Nc1cccc(OCCO)c1
Agent: [Na+]
Product: O=C(Cc1nc(N2CCOCC2)cc(=O)[nH]1)Nc1cccc(OCCO)c1
Yield: 48.3 %

Procedure:
The product is prepared according to the procedure described in Example 5, using 260 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate and 294 mg of 2-(3-aminophenoxy)ethanol in place of the 2,4-difluoroaniline. 180 mg of N-[3-(2-hydroxyethoxy)phenyl]-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide are obtained in the form of a pinkish solid, the characteristics of which are the following:
Reaction SMILES: [NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[CH:5]=[CH:4][C:3]=1C(O)=O.C(O)(=O)C.C(=O)=O>[Zn].O>[NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: Nc1c(C(=O)O)ccc2c1C(=O)c1ccccc1C2=O
Agent: O=C=O
Agent: [Zn]
Solvent: CC(=O)O
Solvent: O
Product: Nc1cccc2c1C(=O)c1ccccc1C2=O
Yield: 112 %

Procedure:
To a three-necked round-bottomed flask equipped with stirrer and reflux condenser was added 5 g (0.014 mole) 1-aminoanthraquinone-2-carboxylic acid, 1 g (0.0037 mole) zinc powder, and 40 ml of 90% acetic acid. The mixture was refluxed gently for 4 hours during which time carbon dioxide was evolved. The reaction mixture was then poured into 200 ml of water and the resulting mixture was heated on a steam bath for 30 minutes. The red solid which precipitated was collected by filtration and washed with water to give 3.5 g (82% yield) of more than 90% pure 1-aminoanthraquinone.
Reaction SMILES: [CH3:1][S:2][C:3]1[C:11]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][N:5]2[N:4]=1.C([Li])CCC.[I:25]CCI.[Cl-].[NH4+]>O1CCCC1>[I:25][C:10]1[N:5]2[N:4]=[C:3]([S:2][CH3:1])[C:11]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:18])[CH3:17])=[C:6]2[CH:7]=[CH:8][CH:9]=1
Reactant: ICCI
Reactant: CSc1nn2ccccc2c1NC(=O)OC(C)(C)C
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Product: CSc1nn2c(I)cccc2c1NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 68.6 %

Procedure:
To a solution of tert-butyl N-[2-methylthiopyrazolo[1,5-a]pyridin-3-yl]carbamate (21.6 g) dissolved in tetrahydrofuran (1 L) was n-butyllithium (1.6M hexane solution; 130 mL) dropwise at −78° C. under a nitrogen stream, and the reaction mixture was stirred for 30 minutes. A solution of 1,2-diiodoethane (24 g) in tetrahydrofuran (50 mL) was added to the obtained reaction mixture, and stirring was continued for 1 hour. After adding saturated aqueous ammonium chloride to the reaction mixture, the temperature was raised to room temperature, extraction was performed with ethyl acetate and the organic extract was washed with water and brine. The obtained organic extract was dried over anhydrous magnesium sulfate and filtered, the solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography and the title compound (21.5 g) was obtained as yellow crystals from the n-hexane:ethyl acetate (5:1) fraction.
Reaction SMILES: B.[Na].[CH2:3]([O:10][C:11]([NH:13][C@H:14]1[CH2:19][CH2:18][C@H:17]([C:20](O)=[O:21])[CH2:16][CH2:15]1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>O1CCCC1>[CH2:3]([O:10][C:11]([NH:13][C@H:14]1[CH2:19][CH2:18][C@H:17]([CH2:20][OH:21])[CH2:16][CH2:15]1)=[O:12])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: O=C(N[C@H]1CC[C@H](C(=O)O)CC1)OCc1ccccc1
Agent: B
Agent: [Na]
Solvent: C1CCOC1
Product: O=C(N[C@H]1CC[C@H](CO)CC1)OCc1ccccc1
Temperature: 0 °C

Procedure:
In 35 ml of tetrahydrofuran was suspended 0.74 g of sodium boron hydride, and boron trifluoride diethyl complex was added to the suspension under ice-cooling. The mixture was stirred as such under ice-cooling for 30 minutes, and 90 ml of a tetrahydrofuran solution containing 3.60 g of trans-4-(benzyloxycarbonylamino)cyclohexanecarboxylic acid was added thereto under ice-cooling. After the mixture was stirred at room temperature for 2 hours, the reaction mixture was poured into an ice water and extracted with chloroform. The extract was washed with water and brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was suspended in diisopropyl ether and collected by filtration to obtain N-benzyloxycarbonyl-trans-4-(hydroxymethyl)cyclohexylamine.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[C:13]([Cl:15])[C:12]([CH2:16]O)=[C:11]([Cl:18])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Br)(Br)[Br:20]>C1COCC1>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([Cl:15])[C:12]([CH2:16][Br:20])=[C:11]([Cl:18])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: BrP(Br)Br
Reactant: OCc1c(Cl)cc(OCc2ccccc2)cc1Cl
Solvent: C1CCOC1
Product: Clc1cc(OCc2ccccc2)cc(Cl)c1CBr
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 89 %

Procedure:
Dissolve (4-benzyloxy-2,6-dichloro-phenyl)-methanol in 2.5 L THF and cool to 0° C. under N2. Add 94.45 g PBr3 dropwise and stir at 0° C. for 30 minutes. Pour the reaction mixture into sat'd. NaHCO3 and extract with EtOAc (2×). Dry over Na2SO4, filter and concentrate under vacuum to yield 269 g (89%) of the title compound as a white solid. MS (electrospray), 345.1, 347.1 (ES−).
Reaction SMILES: [CH3:1][CH:2]([CH3:7])[CH2:3][CH2:4][Mg]Br.[Br:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]Br>O1CCCC1>[CH3:1][CH:2]([CH3:7])[CH2:3][CH2:4][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][Br:8]
Reactant: BrCCCCCCCCCCCBr
Reactant: CC(C)CC[Mg]Br
Solvent: C1CCOC1
Product: CC(C)CCCCCCCCCCCCCBr
Temperature: -10 °C
Reaction time: 1 h

Procedure:
By a procedure analagous to that described in Example 1, 3-methylbutylmagnesium bromide in tetrahydrofuran is reacted with 34.5 g. of 1,11-dibromoundecane and 0.2 g. of Li2CuCl4 in 75 ml. tetrahydrofuran. After one hour stirring at -10° C., the solution is evaporated and the resultant oil is distilled in vacuo to yield the colorless 14-methyl pentadecyl bromide.
Reaction SMILES: [C:1]([O:4][CH:5]1[S:9][C@H:8]([CH2:10][O:11][Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:7][CH2:6]1)(=[O:3])[CH3:2].C(O)(=O)C.[F-].P([O-])(O)(O)=O.[K+]>O1CCCC1.C(OCC)(=O)C>[C:1]([O:4][CH:5]1[S:9][C@@H:8]([CH2:10][OH:11])[CH2:7][CH2:6]1)(=[O:3])[CH3:2]
Reactant: CC(=O)OC1CC[C@@H](CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)S1
Agent: O=P([O-])(O)O
Agent: [F-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(=O)OC1CC[C@H](CO)S1
Reaction time: 5 h
Yield: 71.5 %

Procedure:
To a mixture of 0.54 g of 1-O-acetyl-5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-4thioribofuranose (prepared by the procedure of J. A. Secrist et al., J. Med. Chem.,1992, 35, 533) in 8 ml of tetrahydrofuran and 0.6 g of acetic acid is added 4 mmol of 1M n-tetrabutylamnonium fluoride solution. The reaction is stirred for 5 hours and then another portion of 0.10 g of acetic acid and 1 mmol of n-tetrabutylammonium fluoride is added and the reaction is stirred for 1 hour. Cold potassium dihydrogen phosphate and ethyl acetate are added to the reaction mixture, followed by an aqueous workup. Purification by chromatography gives 0.164 g of the desired product.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([NH:11]C(=O)C)=[C:4]([CH3:15])[CH:3]=1.Cl>O>[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([NH2:11])=[C:4]([CH3:15])[CH:3]=1
Reactant: CC(=O)Nc1c(C)cc(F)cc1[N+](=O)[O-]
Agent: Cl
Solvent: O
Product: Cc1cc(F)cc([N+](=O)[O-])c1N
Yield: 34.3 %

Procedure:
A mixture of N-(4-fluoro-2-methyl-6-nitrophenyl)acetamide (20 g, crude), concentrated hydrochloric acid (100 mL), and H2O (100 mL) was refluxed overnight. The reaction mixture was subsequently extracted with DCM. The organic phase was washed with aqueous NaHCO3 until the pH of the aqueous layer was >7. The organic phase was washed with water and dried over Na2SO4. The solvent was evaporated to give the title compound as a solid (5.5 g, 34%). 1H NMR (400 MHz, CDCl3) δ ppm 7.68 (1H, dd, J1=2.8 Hz, J2=9.2 Hz), 7.05 (1H, dd, J1=2.8 Hz, J2=8.0 Hz), 5.99 (2H, s), 2.19 (3H, s).
Reaction SMILES: [NH2:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([OH:9])=[CH:4][C:3]=1[CH3:10].[H-].[Na+].Cl[C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[C:16]([N:23]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH3:24])[CH:15]=1>CN(C)C=O>[C:28]([O:27][C:25]([N:23]([C:16]1[CH:15]=[C:14]([O:9][C:5]2[CH:6]=[C:7]([CH3:8])[C:2]([NH2:1])=[C:3]([CH3:10])[CH:4]=2)[CH:19]=[CH:18][C:17]=1[N+:20]([O-:22])=[O:21])[CH3:24])=[O:26])([CH3:31])([CH3:29])[CH3:30]
Reactant: CN(C(=O)OC(C)(C)C)c1cc(Cl)ccc1[N+](=O)[O-]
Reactant: Cc1cc(O)cc(C)c1N
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1cc(Oc2ccc([N+](=O)[O-])c(N(C)C(=O)OC(C)(C)C)c2)cc(C)c1N
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
4-Amino-3,5-dimethylphenol (1.10 g) was added to a suspension of sodium hydride (0.35 g, 55% (w/w) dispersion in mineral oil) in anhydrous N,N-dimethylformamide and the mixture was stirred at room temperature for 15 minutes. To the mixture was added in small portions 4-chloro-2-(N-t-butoxycarbonyl-N-methylamino)-nitrobenzene and the mixture was stirred at 120° C. for 1 hour. The reaction mixture was concentrated and the residue was partitioned between ethyl acetate and water The extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was chromatographed on a silica gel column using hexane: ethyl acetate=3:1 the eluant to afford the title compound (2.27 g, Rf=0.24: thin layer chromatography on a silica gel plate using hexane: ethyl acetate=3:1 as the eluant).
Reaction SMILES: [OH:1][C:2]1[C:9]([CH3:10])=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].C(=O)([O-])[O-].[K+].[K+].[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.O>CN(C)C=O>[CH2:17]([O:1][C:2]1[C:9]([CH3:10])=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: Cc1cccc(C=O)c1O
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1cccc(C=O)c1OCc1ccccc1
Temperature: 25 °C
Reaction time: 26 h
Yield: 100.1 %

Procedure:
To a solution of 2-hydroxy-3-methylbenzaldehyde (3.0 g, 22.07 mmol) in N,N-dimethylformamide (50 mL), potassium carbonate (3.65 g, 26.4 mmol) was added and furthermore benzyl bromide (2.9 mL, 24.2 mmol) was added thereto. The mixture was stirred at room temperature for 26 hours, and then water was added thereto and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution and dried (anhydrous magnesium sulfate), and then the solvent was distilled under reduced pressure. The obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:4)] to obtain the title compound (5.0 g, 100%).