Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:22])[N:7]([CH2:19][CH:20]=[CH2:21])[CH:8]([C:12]1[CH:17]=[CH:16][C:15]([Br:18])=[CH:14][CH:13]=1)[CH2:9]C=C)([CH3:4])([CH3:3])[CH3:2]>C(Cl)Cl.Cl[Ru](=CC1C=CC=CC=1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)Cl>[C:1]([O:5][C:6]([N:7]1[CH2:19][CH:20]=[CH:21][CH2:9][CH:8]1[C:12]1[CH:13]=[CH:14][C:15]([Br:18])=[CH:16][CH:17]=1)=[O:22])([CH3:2])([CH3:3])[CH3:4]
Reactant: C=CCC(c1ccc(Br)cc1)N(CC=C)C(=O)OC(C)(C)C
Agent: Cl[Ru](Cl)(=Cc1ccccc1)([P](C1CCCCC1)(C1CCCCC1)C1CCCCC1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CC=CCC1c1ccc(Br)cc1
Yield: 75 %

Procedure:
Allyl-[1-(4-bromo-phenyl)-but-3-enyl]-carbamic acid tert-butyl ester (300 mg, 0.82 mmol) in CH2Cl2 (10 mL) is degassed and the 2nd generation of Grubb's catalyst (40 mg, 5%) is added under N2. The reaction did not proceed at room temperature and the mixture is brought to reflux. TLC is used to determine complete reaction of the olefin. The mixture is loaded onto a column and purified to provide the desired product (208 mg, 75%). 1H NMR (300 MHz, CDCl3) ∂7.43(2H, d, J=8.1 Hz), 7.17-7.26 (2H, m), 5.89-5.95 (1H, m), 5.34-5.58 (2H, m), 4.14-4.36 (1H, m), 3.35-3.44 (1H, m), 2.73-2.81 (1H, m), 2.41-2.62 (1H, m), 1.48 (9H, s).
Reaction SMILES: [OH:1][C:2]1[C:19]([CH2:20][CH:21]=[C:22]([CH3:24])[CH3:23])=[C:18]([O:25][CH3:26])[CH:17]=[C:16]([O:27][CH3:28])[C:3]=1[C:4](=[O:15])[CH:5]=[CH:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1.[OH-].[K+].[H][H].Cl>C(OCC)(=O)C.[Pd].C(O)C>[CH3:26][O:25][C:18]1[CH:17]=[C:16]([O:27][CH3:28])[C:3]([C:4](=[O:15])[CH2:5][CH2:6][C:7]2[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=2)=[C:2]([OH:1])[C:19]=1[CH2:20][CH:21]=[C:22]([CH3:24])[CH3:23]
Reactant: [H][H]
Reactant: COc1ccc(C=CC(=O)c2c(OC)cc(OC)c(CC=C(C)C)c2O)cc1
Agent: [Pd]
Agent: Cl
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CCO
Product: COc1ccc(CCC(=O)c2c(OC)cc(OC)c(CC=C(C)C)c2O)cc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 94.6 %

Procedure:
Then, a liquid mixture of 16.2 g of 2'-hydroxy-4,4',6'-trimethoxy-3'-(3-methyl-2-butenyl)chalcone, 4.0 g of potassium hydroxide and 180 ml of ethanol was added to a suspension of 1.5 g of 5% palladium/carbon in 20 ml of ethyl acetate, in which a hydrogen gas had been sufficiently absorbed in advance, and the mixture was stirred at room temperature in a hydrogen gas atmosphere for 5 hours. After the reaction, the reaction mixture was made acidic by dilute hydrochloric acid, filtered, extracted with ethyl acetate and filtered, and the solvent was removed from the filtrate by distillation. The obtained residue was recrystallized from methanol to obtain 15.4 g (yield=94.6%) of 1-[4,6-dimethoxy-2-hydroxy-3-(3-methyl-2-butenyl)phenyl]-3-(4-methoxyphenyl)-1-propanone in the form of a colorless needle.
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[N:11]1[CH2:15][CH2:14][CH:13]([CH2:16][C:17]3[CH:22]=[CH:21][C:20](Br)=[CH:19][C:18]=3[Cl:24])[C:12]1=[O:25])[CH2:8]2.[OH:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1>>[CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[N:11]1[CH2:15][CH2:14][CH:13]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([C:30]4[CH:31]=[CH:32][C:27]([OH:26])=[CH:28][CH:29]=4)=[CH:19][C:18]=3[Cl:24])[C:12]1=[O:25])[CH2:8]2
Reactant: O=C1C(Cc2ccc(Br)cc2Cl)CCN1C1C2CC3CC(C2)CC1C3
Reactant: OB(O)c1ccc(O)cc1
Product: O=C1C(Cc2ccc(-c3ccc(O)cc3)cc2Cl)CCN1C1C2CC3CC(C2)CC1C3
Yield: 70.7 %

Procedure:
Using the procedure to synthesize Example 81 and using reagents 1-adamantan-2-yl-3-(4-bromo-2-chloro-benzyl)-pyrrolidin-2-one (Example 76) (1.0 g, 2.4 mmol) and 4-hydroxyphenylboronic acid (980 mg, 7.1 mmol) affords 740 mg (72%) of the title compound: Mass spectrum (apci) m/z=436.2 (M+H).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[C:11]3=[CH:20][C:21]([CH2:23][N:24]([CH3:26])[CH3:25])=[CH:22][N:10]3[N:9]=2)=[CH:4][CH:3]=1.[CH2:27]([N:29]=[C:30]=[O:31])[CH3:28]>ClCCl>[CH2:27]([NH:29][C:30]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([N:14]3[CH2:15][CH2:16][O:17][CH2:18][CH2:19]3)[C:11]3=[CH:20][C:21]([CH2:23][N:24]([CH3:26])[CH3:25])=[CH:22][N:10]3[N:9]=2)=[CH:4][CH:3]=1)=[O:31])[CH3:28]
Reactant: CN(C)Cc1cc2c(N3CCOCC3)nc(-c3ccc(N)cc3)nn2c1
Reactant: CCN=C=O
Solvent: ClCCl
Product: CCNC(=O)Nc1ccc(-c2nc(N3CCOCC3)c3cc(CN(C)C)cn3n2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Compound 13a (0.15 mmol) was dissolved in 10 mL of anhydrous dichloromethane, and 3 equiv of ethyl isocyanate was added and stirred at room temperature overnight. The target compound was obtained by filtration.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[N:12]([C:13]([C:15]2[S:19][C:18]([C:20]3[CH:27]=[CH:26][C:23]([CH:24]=O)=[CH:22][CH:21]=3)=[CH:17][CH:16]=2)=[O:14])[N:11]=[C:10]([C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)[CH2:9]1.[NH:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.O.Cl>[N:30]1[CH:31]=[CH:32][CH:33]=[C:28]([C:10]2[CH2:9][CH:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[OH:1])[N:12]([C:13]([C:15]3[S:19][C:18]([C:20]4[CH:27]=[CH:26][C:23]([CH2:24][N:34]5[CH2:38][CH2:37][CH2:36][CH2:35]5)=[CH:22][CH:21]=4)=[CH:17][CH:16]=3)=[O:14])[N:11]=2)[CH:29]=1
Reactant: O=Cc1ccc(-c2ccc(C(=O)N3N=C(c4cccnc4)CC3c3ccccc3O)s2)cc1
Reactant: C1CCNC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: O=C(c1ccc(-c2ccc(CN3CCCC3)cc2)s1)N1N=C(c2cccnc2)CC1c1ccccc1O
Temperature: 25 °C
Reaction time: 72 h
Yield: 26.1 %

Procedure:
To a solution of 4-(5-{[5-(2-hydroxyphenyl)-3-pyridin-3-yl-4,5-dihydro-1H-pyrazol-1-yl]carbonyl}-2-thienyl)benzaldehyde (0.205 g, 0.452 mmol) in THF (72 mL) was added pyrrolidine (0.042 mL, 0.50 mmol) and sodium triacetoxyborohydride (0.105 g, 0.497 mmol). The reaction mixture was allowed to stir at rt for 3 days. The solution was diluted with water and 1N aqueous HCl and extracted with EtOAc. The organic solutions were combined, washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography to give 2-[3-pyridin-3-yl-1-({5-[4-(pyrrolidin-1-ylmethyl)phenyl]-2-thienyl}carbonyl)-4,5-dihydro-1H-pyrazol-5-yl]phenol (I-56) (0.060 g, 0.118 mmol) as a white solid. LCMS: (FA) ES+ 509.4. 1H NMR (400 MHz, d6-DMSO) δ: 10.76-10.86 (bs, 1H), 9.74-9.82 (bs, 1H), 9.11 (s, 1H), 8.71-8.77 (m, 1H), 8.36-8.42 (m, 1H), 8.03-8.08 (m, 1H), 7.84-7.90 (m, 2H), 7.62-7.73 (m, 2H), 7.08 (t, 1H), 6.92-6.97 (m, 1H), 6.82-6.88 (m, 1H), 6.72 (t, 1H), 5.82-5.89 (m, 1H), 4.34-4.39 (m, 2H), 3.86-3.98 (m, 1H), 3.31-3.41 (m, 2H), 3.18-3.25 (m, 1H), 3.00-3.12 (m, 2H), 1.96-2.07 (m, 2H), and 1.82-1.94 (m, 2H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][C:3]=1[NH:11][C:12](=[O:21])[CH:13]=[CH:14][C:15]1[CH:16]=[N:17][CH:18]=[N:19][CH:20]=1.C(O)C.[Cl-].[NH4+].C(=O)([O-])[O-].[K+].[K+]>[Fe].O>[NH2:8][C:5]1[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([NH:11][C:12](=[O:21])[CH:13]=[CH:14][C:15]2[CH:20]=[N:19][CH:18]=[N:17][CH:16]=2)[CH:4]=1
Reactant: Cc1ccc([N+](=O)[O-])cc1NC(=O)C=Cc1cncnc1
Agent: [Fe]
Agent: O=C([O-])[O-]
Agent: [Cl-]
Solvent: O
Solvent: CCO
Product: Cc1ccc(N)cc1NC(=O)C=Cc1cncnc1
Temperature: 70 °C

Procedure:
1.42 g of the product of step 4 was added to a mixture of ethanol (90 ml) and water (30 ml), and then 2.24 g of iron powder and 0.80 g of ammonium chloride were added. After addition, the solution was heated to 70° C. and reacted for 30 min. The completion of reaction was indicated by TLC. The reaction mixture was filtered. The filter cake was washed with hot ethanol repeatedly. The filtrate was concentrated under reduced pressure to give a yellow solid. Then 20 ml of potassium carbonate solution (10%) was added to the solid. The mixture was stirred, left to stand, filtered, and dried to give a solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[C:5]([O:11][CH3:12])[C:4]=1[NH:13][C:14]([CH:16]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)C(O)=O)=[O:15].C(N1C=CN=C1)(N1C=CN=C1)=O.[C:38]([NH:52][NH2:53])(=[O:51])[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH3:50]>C1COCC1>[O:15]=[C:14]([NH:13][C:4]1[C:5]([O:11][CH3:12])=[CH:6][C:7]([O:9][CH3:10])=[CH:8][C:3]=1[O:2][CH3:1])[CH:16]([CH:39]([CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH3:50])[C:38]([NH:52][NH2:53])=[O:51])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: COc1cc(OC)c(NC(=O)C(C(=O)O)c2ccccc2)c(OC)c1
Reactant: CCCCCCCCCCCCC(=O)NN
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: CCCCCCCCCCCC(C(=O)NN)C(C(=O)Nc1c(OC)cc(OC)cc1OC)c1ccccc1
Temperature: 25 °C
Reaction time: 17 h

Procedure:
A solution of α-[[(2,4,6-trimethoxyphenyl)amino]-carbonyl]-benzene acetic acid (46.73 g, 0.1353 mol), and 1,1'-carbonyldiimidazole (24.7 g, 0.152 mol) in dry THF (1.0 L) was stirred at room temperature under nitrogen for 2 hours. A white solid precipitated. To the suspension was added tridecanoic acid hydrazide (30.90 g, 0.1353 mol), and the mixture was stirred at room temperature for 17 hours, then at 40° C. for 21 hours. The mixture was chilled (+5° C.) and filtered. The filtercake was washed (THF, ether, water) and dried under house vacuum/air stream; yield 54.36 g (72%); mp 175°-180° C.
Reaction SMILES: [CH2:1]([O:3][C:4]1[C:9]([CH:10]([CH3:12])[CH3:11])=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:13][OH:14])[CH3:2]>C1C=CC=CC=1.O=[Mn]=O>[CH2:1]([O:3][C:4]1[C:9]([CH:10]([CH3:11])[CH3:12])=[CH:8][CH:7]=[CH:6][C:5]=1[CH:13]=[O:14])[CH3:2]
Reactant: CCOc1c(CO)cccc1C(C)C
Agent: O=[Mn]=O
Solvent: c1ccccc1
Product: CCOc1c(C=O)cccc1C(C)C
Reaction time: 48 h
Yield: 42.6 %

Procedure:
MnO2 (9.49 g, 109 mmol) was added to a stirring solution of (2-ethoxy-3-isopropylphenyl)methanol (3.54 g, 18.2 mmol) in benzene (175 mL) under N2. After stirring for 48 h, the solution was filtered over diatomaceous earth and the pad rinsed with CH2Cl2 (200 mL), and the solution was concentrated to a clear oil. Purification by column chromatography (silica gel, hexanes/EtOAc, 100 to 98:2) gave the title compound (1.49 g, 42%) as a light yellow oil: 1H NMR (300 MHz, DMSO-d6) δ 10.26 (s, 1H), 7.67 (dd, J=7.6, 1.7 Hz, 1H), 7.59 (dd, J=7.6, 1.7 Hz, 1H), 7.28 (t, J=7.6 Hz, 1H), 3.97 (q, J=6.9 Hz, 2H), 3.32-3.30 (m, 1H), 1.39 (t, J=6.9 Hz, 3H), 1.21 (d, J=6.9 Hz, 6H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][C:11](O)=[O:12])=[CH:5][CH:4]=1.CC(C[AlH]CC(C)C)C.[NH4+].[Cl-]>C1(C)C=CC=CC=1.C(=O)=O.CC(C)=O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH2:10][CH:11]=[O:12])=[CH:5][CH:4]=1
Reactant: COc1ccc(CCC(=O)O)cc1
Agent: CC(C)C[AlH]CC(C)C
Agent: O=C=O
Agent: [Cl-]
Solvent: Cc1ccccc1
Solvent: CC(C)=O
Product: COc1ccc(CCC=O)cc1
Temperature: -78 °C
Reaction time: 2 h
Yield: 70.7 %

Procedure:
3-(4-Methoxy-phenyl)-propionic acid (9a, 1.80 g, 10.0 mmol) in toluene (25.0 mL) was cooled to −78° C. in dry ice-acetone bath for 5-10 minutes under N2. DIBAL-H (11.0 mmol) was slowly added by syringe and stirred for 2 hours at −78° C. Then, the reaction mixture was poured quickly into an aqueous NH4Cl solution with vigorous stirring. The solution was extracted twice with ether and the organic layer was washed with brine, dried over MgSO4(s), and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel to provide 3-(4-methoxy-phenyl)-propionaldehyde (9b, 1.16 g, 7.07 mmol) as yellow oil in 70.7% yield.
Reaction SMILES: [OH:1][C:2]1([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[CH:9]=2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C([O-])([O-])=O.[K+].[K+].[CH2:24](Br)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CN(C=O)C>[CH2:24]([N:5]1[CH2:6][CH2:7][C:2]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:15])[F:16])[CH:9]=2)([OH:1])[CH2:3][CH2:4]1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: BrCc1ccccc1
Reactant: OC1(c2cccc(C(F)(F)F)c2)CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: OC1(c2cccc(C(F)(F)F)c2)CCN(Cc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 92.5 %

Procedure:
To a mixture of 24.5 g of 4-hydroxy-4-[3-(trifluoromethyl)phenyl]piperidine (commercial) and 27.6 g of K2CO3 in 20 ml of DMF is added dropwise, at rt, 17.1 g of benzyl bromide, and the mixture is then heated at 40° C. for 2 hours and stirred overnight at rt. The reaction mixture is concentrated under vacuum, the residue is taken up in water and extracted with EtOAc, the organic phase is washed with water and dried over Na2SO4, and the solvent is evaporated off under vacuum. 31 g of the expected product are obtained.
Reaction SMILES: ClC(Cl)(Cl)C(Cl)(Cl)Cl.C(N(CC)CC)C.[CH2:16]([O:23][CH2:24][C:25]([NH:27][NH:28][C:29]([C@H:31]1[CH2:36][CH2:35][C@H:34]([NH:37][C:38](=[O:47])[O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH2:33][CH2:32]1)=[O:30])=O)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[CH2:16]([O:23][CH2:24][C:25]1[O:30][C:29]([C@H:31]2[CH2:36][CH2:35][C@H:34]([NH:37][C:38](=[O:47])[O:39][CH2:40][C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=3)[CH2:33][CH2:32]2)=[N:28][N:27]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=C(COCc1ccccc1)NNC(=O)[C@H]1CC[C@H](NC(=O)OCc2ccccc2)CC1
Agent: ClC(Cl)(Cl)C(Cl)(Cl)Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(N[C@H]1CC[C@H](c2nnc(COCc3ccccc3)o2)CC1)OCc1ccccc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
Hexachloroethane (205 mg, 0.87 mmol), triethylamine (0.29 ml, 2.08 mmol), and the compound (152 mg, 0.35 mmol) obtained in Step 1 above were added to a dichloromethane (9 ml) solution of triphenylphosphine (273 mg, 1.04 mmol) under ice cooling and the resulting mixture was stirred at room temperature for 24 hours. The reaction mixture was diluted with dichloromethane:methanol [10:1 (v/v)], washed with 10% aqueous citric acid solution, and dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure and the residue was purified by silica gel column chromatography [n-hexane:ethyl acetate=2:1→1:1 (v/v)] to give 125 mg (86%) of the title compound as a colorless solid.
Reaction SMILES: N[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH3:12])[CH:7]2[CH3:13].N([O-])=[O:15].[Na+].[Na+].[Cl-]>OS(O)(=O)=O>[OH:15][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH3:12])[CH:7]2[CH3:13]
Reactant: CC1c2cccc(N)c2C(=O)N1C
Reactant: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Cl-]
Agent: [Na+]
Product: CC1c2cccc(O)c2C(=O)N1C
Temperature: -10 °C
Reaction time: 0.25 h

Procedure:
7-amino-2,3-dimethyl-2,3-dihydro-isoindol-1-one (11.45 g) is suspended in a mixture of ice (27 g) and H2SO4 conc. (9.70 mL) and cooled to −10° C. Aqueous sodium nitrite solution (2.5 molar, 31.18 mL) is added dropwise, so that the temperature does not rise above 0° C. and the solution is stirred for 15 min at this temperature. Then H20 (135 mL) is added and the solution is heated to 80° C. for 15 min. For working up it is combined with 10% NaCl solution (100 mL) and extracted twice with 100 mL of CH2Cl2. The organic phase is extracted with NaOH solution (0.2 molar) and then the aqueous phase is acidified (HCl aq. conc.) and re-extracted with CH2Cl2. The organic phase is dried on magnesium sulphate, filtered off from the desiccant and the solvent is eliminated in vacuo.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:15]=[CH:14][C:9]([C:10]([O:12]C)=[O:11])=[CH:8][C:7]=1[N+:16]([O-:18])=[O:17])[CH:2]([CH3:4])[CH3:3].[OH-].[Na+]>CO.C1COCC1>[CH2:1]([O:5][C:6]1[CH:15]=[CH:14][C:9]([C:10]([OH:12])=[O:11])=[CH:8][C:7]=1[N+:16]([O-:18])=[O:17])[CH:2]([CH3:4])[CH3:3]
Reactant: COC(=O)c1ccc(OCC(C)C)c([N+](=O)[O-])c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)COc1ccc(C(=O)O)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 18 h
Yield: 97.8 %

Procedure:
Methyl 4-isobutyloxy-3-nitrobenzoate (2.50 g, 9.87 mmol) was dissolved in a mixture of methanol (10 mL) and 25 THF (10 mL). After addition of 2M aqueous sodium hydroxide (7.5 mL, 15.0 mmol), the solution was stirred for 18 hours at room temperature. The solvent was distilled off under reduced pressure, and were added to the residue water (20 mL) and 3M aqueous hydrochloric acid to adjust 30 the solution to pH 1. The precipitated crystalline product was collected by filtration. The crystalline product was washed with water (20 mL×2) and dried at 50° C. for 4 hours under reduced pressure, to give 2.31 g (yield 98%) of the desired compound in the form of a white crystalline product.
Reaction SMILES: [OH:1][P:2]([CH2:5][CH:6]([CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:7]([O:9]CC1C=CC=CC=1)=[O:8])([CH3:4])=[O:3]>C(O)C.[Pd]>[OH:3][P:2]([CH2:5][CH:6]([CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:7]([OH:9])=[O:8])([CH3:4])=[O:1]
Reactant: CP(=O)(O)CC(CCc1ccccc1)C(=O)OCc1ccccc1
Agent: [Pd]
Solvent: CCO
Product: CP(=O)(O)CC(CCc1ccccc1)C(=O)O
Temperature: 25 °C
Reaction time: 20 h
Yield: 109.3 %

Procedure:
Benzyl 2-((hydroxy(methyl)phosphinyl)methyl)-4-phenylbutanoate (433 mg, 1.25 mmol) was dissolved in 95% ethanol (8.0 mL) and catalyst (130 mg of 10% palladium on carbon) was added. After being stirred under hydrogen (1 atm.) for 20 h at room temperature, the mixture was filtered through a 1-cm plug of Celite with additional 95% ethanol (2×10 mL). Evaporation of the filtrate gave 350 mg of a colorless oil used directly in Step C.
Reaction SMILES: C[O:2][C@H:3]1[C@H:8]([OH:9])[C@@H:7]([O:10][C@H:11]2[O:16][C:15](C(O)=O)=[CH:14][C@H:13]([OH:20])[C@H:12]2[OH:21])[C@H:6]([O:22]C)[O:5][CH2:4]1.[O:24]=C[C@@H]([C@H]([C@@H](CO)O)O)O>>[CH2:15]1[O:16][C@@H:11]([O:10][C@@H:7]([C@H:8]([OH:9])[C@@H:3]([OH:2])[CH:4]=[O:5])[CH2:6][OH:22])[C@H:12]([OH:21])[C@@H:13]([OH:20])[C@@H:14]1[OH:24]
Reactant: CO[C@@H]1OC[C@@H](OC)[C@H](O)[C@H]1O[C@H]1OC(C(=O)O)=C[C@H](O)[C@H]1O
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)CO
Product: O=C[C@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC[C@@H](O)[C@H](O)[C@H]1O

Procedure:
The xylobiose or xylotriose liberated in the hydrolysis reaction was detected by developing the plate as follows: The plate was air-dried for appr. 10 minutes. After this the plate was sprayed with the developer (10% H2O, 10% conc. H2SO4, 80% ethanol and 0.2% 3.5-dihydroxytoluene, orcin: Merck 820933). The plate was dried (appr. 10 min on a paper) and developed by incubating it at 105-110° C. for 10 min. The xylobiose (and xylose, in the presence of β-xylosidase in the enzyme sample) formed could be detected as a coloured dot at the same distance from the starting line as the standard sugars (1-5 μl of 0.2% aqueous solution applied similarly to the hydrolysate). Thus the bond between hexenuronic acid and xylose was broken by hexenuronidase activity present in the enzyme sample, resulting in the release of free xylobiose.
Reaction SMILES: [CH3:1][C:2]1([CH3:22])[CH2:6][C:5]2[CH:7]=[CH:8][CH:9]=[C:10]([CH2:11][CH:12]3[CH2:21][CH2:20][C:15]4([O:19][CH2:18][CH2:17][O:16]4)[CH2:14][CH2:13]3)[C:4]=2[O:3]1>[Pd].C(O)C>[CH3:1][C:2]1([CH3:22])[CH2:6][C:5]2[CH:7]=[CH:8][CH:9]=[C:10]([CH:11]=[C:12]3[CH2:21][CH2:20][C:15]4([O:19][CH2:18][CH2:17][O:16]4)[CH2:14][CH2:13]3)[C:4]=2[O:3]1
Reactant: CC1(C)Cc2cccc(CC3CCC4(CC3)OCCO4)c2O1
Agent: [Pd]
Solvent: CCO
Product: CC1(C)Cc2cccc(C=C3CCC4(CC3)OCCO4)c2O1

Procedure:
This compound is prepared in a manner analogous to that of Step C of Example 2, by the hydrogenation of 7.8 grams (0.026 mole) of 8-(2,3-dihydro-2,2-dimethylbenzofuran-7-ylmethylene)-1,4-dioxaspiro[4.5]decane in the presence of 0.4 gram (catalyst) of 10% palladium on charcoal in 50 mL of ethanol, yielding 8-(2,3-dihydro-2,2-dimethylbenzofuran-7-ylmethyl)-1,4-dioxaspiro[4.5]decane.
Reaction SMILES: C[O:2][C:3]1[C:4]([CH3:20])=[C:5]([C:14]([CH3:19])=[C:15]([O:17]C)[CH:16]=1)[C:6]([O:8][CH2:9][C:10]([Cl:13])([Cl:12])[Cl:11])=[O:7]>C(Cl)Cl>[OH:2][C:3]1[C:4]([CH3:20])=[C:5]([C:14]([CH3:19])=[C:15]([OH:17])[CH:16]=1)[C:6]([O:8][CH2:9][C:10]([Cl:11])([Cl:12])[Cl:13])=[O:7]
Reactant: COc1cc(OC)c(C)c(C(=O)OCC(Cl)(Cl)Cl)c1C
Solvent: ClCCl
Product: Cc1c(O)cc(O)c(C)c1C(=O)OCC(Cl)(Cl)Cl
Temperature: 0 °C
Reaction time: 2.5 h

Procedure:
A solution of 2.73 g of 2,2,2-trichloroethyl 3,5-dimethoxy-2,6-dimethylbenzoate in 8 ml of methylene chloride was cooled to -78° C., whereupon the dissolved material partly precipitated. To the stirred mixture a solution of 6.01 g of boron tribromide in 8 ml of methylene chloride was added dropwise within 20 minutes. During the addition a clear solution formed, but later on a precipitate formed again. After stirring for 10 minutes at -78° C. and for 2.5 hours at 0° C., the reaction mixture was poured on ice water with stirring, and the aqueous layer was extracted with methylene chloride. The organic layer was washed with water, dried over sodium sulphate and evaporated to dryness in vacuo. The residue was chromatographed on silica gel using acetone/n-hexane (1:3, v/v) for the elution. Crystallization of the purified product from ethyl acetate/n-hexane afforded 2,2,2-trichloroethyl 3,5-dihydroxy-2,6-dimethylbenzoate as white crystals with mp 132°-133° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:18])[C:4]1[CH:16]=[C:15](I)[CH:14]=[C:6]([C:7]([N:9]([CH3:13])[CH2:10][CH2:11][CH3:12])=[O:8])[CH:5]=1.[F:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[CH3:1][O:2][C:3]([C:4]1[CH:16]=[C:15]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[F:19])[CH:14]=[C:6]([C:7](=[O:8])[N:9]([CH3:13])[CH2:10][CH2:11][CH3:12])[CH:5]=1)=[O:18]
Reactant: CCCN(C)C(=O)c1cc(I)cc(C(=O)OC)c1
Reactant: OB(O)c1ccccc1F
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Product: CCCN(C)C(=O)c1cc(C(=O)OC)cc(-c2ccccc2F)c1
Temperature: 25 °C
Yield: 45.1 %

Procedure:
Add 1,4-dioxane (10 mL), 5-iodo-N-methyl-N-propyl-isophthalamic acid methyl ester (0.720 g, 2.00 mmol), 2-fluorophenylboronic acid (0.364 g, 2.60 mmol), tetrakis(triphenylphosphine)palladium (0) (0.347 g, 0.300 mmol), and potassium carbonate (0.829 g, 6.00 mmol) to a sealed flask flushed with nitrogen. Heat the mixture overnight and cool to room temperature. Filter the mixture though a filtering agent, concentrate and purify (silica gel chromatography, eluting with 4:96 ethyl acetate:hexanes) to give the title compound (0.297 g, 45%).
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6](=[O:26])[CH:7]([C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-])=O)=[C:14]([O:21][CH2:22][CH:23]3[CH2:25][CH2:24]3)[CH:13]=2)[CH2:8][CH:9]([CH3:11])[CH3:10])[CH2:3][CH2:2]1>CC(O)=O.O.[Zn]>[CH:1]1([CH2:4][O:5][C:6](=[O:26])[CH:7]([C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[C:14]([O:21][CH2:22][CH:23]3[CH2:25][CH2:24]3)[CH:13]=2)[CH2:8][CH:9]([CH3:11])[CH3:10])[CH2:3][CH2:2]1
Reactant: CC(C)CC(C(=O)OCC1CC1)c1ccc([N+](=O)[O-])c(OCC2CC2)c1
Agent: [Zn]
Solvent: CC(=O)O
Solvent: O
Product: CC(C)CC(C(=O)OCC1CC1)c1ccc(N)c(OCC2CC2)c1
Yield: 73.7 %

Procedure:
2-(3-Cyclopropylmethoxy-4-nitro-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester (34.0 g, 94.2 mmol) was dissolved in AcOH (300 mL) and water (20 mL). Then, Zn powder (60.0 g, 923 mmol) was added in portions. The reaction mixture was refluxed for 1 h and after cooling the precipitate was filtered. The solvent was evaporated and water (150 mL) was added. The reaction mixture was extracted with EtOAc (3×100 mL) and the combined organic phases were washed with water (3×100 mL) and brine (100 mL). Drying of the organic phase was performed with magnesium sulfate. The evaporation of the solvent gave crude product as a brown oil, which was purified by silica gel gradient column chromatography by use of Heptane-EtOAc to give 2-(4-amino-3-cyclopropylmethoxy-phenyl)-4-methyl-pentanoic acid cyclopropylmethyl ester as a yellow oil (23 g, 75%). 1H NMR (300 MHz, CDCl3/TMS): δ 6.73-6.61 (m, 3H), 3.94-3.78 (m, 6H), 3.53 (t, J=7.7 Hz, 1H), 1.94-1.85 (m, 1H), 1.65-1.56 (m, 1H), 1.52-1.43 (m, 1H), 1.28-1.18 (m, 1H), 1.11-1.03 (m, 1H), 0.90 (d, J=6.6 Hz, 6H), 0.64-0.58 (m, 2H), 0.53-0.47 (m, 2H), 0.36-0.33 (m, 2H), 0.24-0.21 (m, 2H); 13C NMR (75 MHz, CDCl3/TMS): δ 174.6, 146.4, 135.3, 129.3, 120.5, 114.6, 111.2, 73.1, 69.0, 49.2, 42.7, 25.8, 22.6, 22.4, 10.4, 9.8, 3.2.