Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC1[CH:12]=[CH:11][C:8]([CH:9]=[CH2:10])=[CH:7][CH:6]=1)(=O)C.[OH-].[K+].C(O[C:20]([O:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=O)(C)(C)C>[OH-].[K+].CO>[C:26]([O:25][C:23]([O:22][C:20]1[CH:10]=[CH:9][C:8]([CH:11]=[CH2:12])=[CH:7][CH:6]=1)=[O:24])([CH3:27])([CH3:28])[CH3:29]
Reactant: C=Cc1ccc(OC(C)=O)cc1
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: C=Cc1ccc(OC(=O)OC(C)(C)C)cc1
Temperature: 12 °C
Yield: 83.2 %

Procedure:
A solution comprising 2.4 g of potassium hydroxide, 201 g 4-acetoxystyrene and 500 g of methanol was heated at reflux for 2.2 hours. The reaction was cooled to 12° C. and 64 g potassium hydroxide pellets were added over a period of 10 minutes. After warming to 25° C., 314 g di-tertiary-butyl-dicarbonate was introduced over a period of one hour. After an additional 2.3 hours of reaction time, the reaction slurry was washed with water and extracted with ethyl acetate. The ethyl acetate was stripped from the extraction mixture using a rotary evaporator, and the residual oil was charged with 0.26 g phenothiazine inhibitor. Distillation at 0.1 mm Hg yielded 227.2 g (85% yield) 4-tertiary-butoxycarbonyloxystyrene (IV).
Reaction SMILES: [CH3:1][C:2]1[C:9]2[C:8]([CH3:10])=[CH:7][S:6][C:5]=2[S:4][C:3]=1[CH:11]=O.[CH3:13][CH:14]([CH3:30])[C:15]([NH:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)[CH:19]=1)=[O:16]>>[CH3:1][C:2]1[C:9]2[C:8]([CH3:10])=[CH:7][S:6][C:5]=2[S:4][C:3]=1[CH2:11][N:27]1[CH2:28][CH2:29][CH:24]([C:20]2[CH:19]=[C:18]([NH:17][C:15](=[O:16])[CH:14]([CH3:13])[CH3:30])[CH:23]=[CH:22][CH:21]=2)[CH2:25][CH2:26]1
Reactant: CC(C)C(=O)Nc1cccc(C2CCNCC2)c1
Reactant: Cc1csc2sc(C=O)c(C)c12
Product: Cc1csc2sc(CN3CCC(c4cccc(NC(=O)C(C)C)c4)CC3)c(C)c12

Procedure:
Prepared by Procedure F and Scheme R using 3,4-dimethylthieno[2,3-b)thiophene-2-carbaldehyde and 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide: ESMS m/e: 427.1 (M+H)+.
Reaction SMILES: C([Li])CCC.C(NC(C)C)(C)C.[C:13]([O:17][C:18]([NH:20][C@H:21]([C@H:29]1[O:33][C:32](=[O:34])[CH2:31][CH2:30]1)[CH2:22][CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].[C:35]1(=[O:41])[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1.[Cl-].[NH4+]>O1CCCC1.CCCCCC>[C:13]([O:17][C:18]([NH:20][C@H:21]([C@H:29]1[O:33][C:32](=[O:34])[C@H:31]([C:35]2([OH:41])[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]2)[CH2:30]1)[CH2:22][CH:23]1[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]
Reactant: CC(C)(C)OC(=O)N[C@@H](CC1CCCCC1)[C@@H]1CCC(=O)O1
Reactant: O=C1CCCCC1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@@H](CC1CCCCC1)[C@@H]1C[C@@H](C2(O)CCCCC2)C(=O)O1
Reaction time: 0.5 h
Yield: 62.2 %

Procedure:
1.43 ml (3.58 mmoles) of butyllithium (as a 2.5M hexane solution) was added dropwise, at -78° C. and under an atmosphere of nitrogen, to a solution of 0.50 ml (3.57 mmoles) of diisopropylamine in 10 ml of anhydrous tetrahydrofuran. The mixture was then stirred for 30 minutes, after which a solution of 500 mg (1.61 mmoles) of (5S)-5-[(1S)-1-(N-t-butoxycarbonylamino)-2-cyclohexylethyl]dihydrofuran-2(3H)-one (prepared as described in Preparation 5) in 5 ml of anhydrous tetrahydrofuran was added thereto. The mixture was then stirred for a further 1 hour, and then 0.24 ml (3.55 mmoles) of distilled cyclohexanone was added to the mixture and stirred for 2 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, which was then extracted with ethyl acetate. The extract was washed with a 10% w/v aqueous solution of citric acid, with water and with a saturated aqueous solution of sodium chloride, in that order. It was then dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by medium pressure silica gel column chromatography (using a 1:1 by volume mixture of hexane and diethyl ether as eluent), followed by recrystallization from hexane, to give 410 mg (yield 62%) of the title compound as white crystals, melting at 133°-134° C.
Reaction SMILES: C(O)(C(F)(F)F)=O.[CH2:8]([O:43][CH:44]1[C@H:48]2[C@H:49](OC3CCCCO3)[N:50](C(OC(C)(C)C)=O)[C:51]3[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[CH:55][C:52]=3[C:53](=[O:54])[N:47]2[CH2:46][CH2:45]1)[CH2:9][CH2:10][O:11][CH:12]1[C@H:16]2[C@H:17](OC3CCCCO3)[N:18](C(OC(C)(C)C)=O)[C:19]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][C:20]=3[C:21](=[O:22])[N:15]2[CH2:14][CH2:13]1.C([O-])(O)=O.[Na+]>CO.C(Cl)(Cl)Cl>[CH2:8]([O:43][CH:44]1[C@@H:48]2[CH:49]=[N:50][C:51]3[CH:58]=[CH:57][C:56]([O:59][CH3:60])=[CH:55][C:52]=3[C:53](=[O:54])[N:47]2[CH2:46][CH2:45]1)[CH2:9][CH2:10][O:11][CH:12]1[C@@H:16]2[CH:17]=[N:18][C:19]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][C:20]=3[C:21](=[O:22])[N:15]2[CH2:14][CH2:13]1
Reactant: COc1ccc2c(c1)C(=O)N1CCC(OCCCOC3CCN4C(=O)c5cc(OC)ccc5N(C(=O)OC(C)(C)C)[C@@H](OC5CCCCO5)[C@H]34)[C@H]1[C@H](OC1CCCCO1)N2C(=O)OC(C)(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: ClC(Cl)Cl
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc2c(c1)C(=O)N1CCC(OCCCOC3CCN4C(=O)c5cc(OC)ccc5N=C[C@@H]34)[C@@H]1C=N2
Reaction time: 1 h
Yield: 62.5 %

Procedure:
95% TFA (3 mL) was added drop-wise to dimer compound 15a (75 mg, 0.08 mmol) at 0° C. This was then stirred for 1 h and the mixture was poured into saturated NaHCO3 (30 mL) solution to naturalize the reaction mixture. The mixture was extracted with chloroform (3×20 mL). The organic layer was then washed water (20 mL), brine (20 mL) then dried (MgSO4) and filtrated. The excess solvent was removed under reduced pressure to give the crude product, which was subjected to flash column chromatography (SiO2, 2% methanol-chloroform). Removal of excess eluent under reduced pressure without heating afforded the final product 16a (30 mg, 0.05 mmol, 70%) as a solid: [α]20D=+477° (c=0.11, CHCl3); 1H NMR (CDCl3, 400 MHz): δ 2.01-2.06 (m, 4H, 2-H, 2′-H), 2.28-2.31 (m, 4H, 1-H, 1′-H), 2.39-2.42 (m, 2H, 13-H), 3.55-3.60 (m, 2H, 3-H, 3′-H), 3.67-3.73 (m, 2H, 11a-H, 11a′-H), 3.77-3.87 (m, 2H, 3-H, 3′-H), 3.91 (s, 6H, 7-OMe, 7′-OMe), 4.23-4.31 (m, 4H, 12-H, 12′-H), 6.84 (s, 2H, 9-H, 9′-H), 7.50 (s, 2H, 6-H, 6′-H), 7.64 (d, 2H, J=4, 11-H, 11′-H); 13C NMR (CDCl3, 400 MHz): δ 24.1, 28.4, 29.6, 46.6, 53.6, 56.1, 58.4, 65.4, 110.8, 111.6, 120.4, 140.6, 147.8, 150.6, 162.3, 164.6; IR (neat): 3350, 2951, 1600, 1505, 1434, 1262, 1217, 1021 cm−1; MS (FAB) m/z (relative intensity) 597 ([M+2×MeOH]+., 16), 565 ([M+MeOH]+., 5), 533 (M+., 100).
Reaction SMILES: [CH2:1](Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:9][CH2:10][CH2:11][NH:12][CH2:13][CH2:14][OH:15].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1>[OH:9][CH2:10][CH2:11][N:12]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH2:13][CH2:14][OH:15]
Reactant: ClCc1ccccc1
Reactant: OCCNCCO
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: OCCN(CCO)Cc1ccccc1

Procedure:
The process according to claim 2 which comprises adding one molar equivalent of benzyl chloride to a warmed mixture containing one molar equivalent of N,N-bis(2-hydroxyethyl)amine and one molar equivalent of sodium carbonate, the addition rate of benzyl chloride being so as to maintain the exothermic reaction temperature at about 70° to 100° C.; maintaining the reaction temperature at about 70° to 100° C. for a short period; adding toluene to the reaction mixture; cooling the mixture to about 50° to 65° C.; filtering the mixture to remove inorganics; washing the filter-cake with toluene; drving the combined filtrate and washings by azeotropic distillation to produce a dry toluene solution containing a substantially quantitative yield of N,N-bis(2-hydroxyethyl)benzylamine.
Reaction SMILES: C[O:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([O:13]C)=[CH:5][C:4]=1/[CH:15]=[C:16](\[CH3:20])/[C:17]([OH:19])=[O:18].[N+]([O-])(O)=O>C(OCC)(=O)C.CC(O)=O>[C:3]1(=[O:2])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](=[O:13])[CH:5]=[C:4]1/[CH:15]=[C:16](\[CH3:20])/[C:17]([OH:19])=[O:18]
Reactant: COc1cc(/C=C(\C)C(=O)O)c(OC)c2ccccc12
Solvent: O=[N+]([O-])O
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: C/C(=C\C1=CC(=O)c2ccccc2C1=O)C(=O)O
Temperature: 25 °C
Reaction time: 4 h
Yield: 57.3 %

Procedure:
Following modified procedures of Shinkawa et al. and Flader et al.16,22 the acid 29a (0.114 g, 0.419 mmol) was dissolved in ethyl acetate (10 mL) at room temperature, then HNO3 (1.0 mL) and AcOH (3 drops) were added at room temperature. The reaction was stirred at room temperature for 4 hours before being diluted with ethyl acetate and washed with brine. The organic layer was dried over MgSO4, filtered, and condensed. The yellow oil was then purified by either flash column chromatography (2:3 Et2O:hexanes 0.5% AcOH) or recrystallization from Et2O/hexanes to afford 30a (0.059 g, 0.24 mmol, 58%) as a yellow solid.
Reaction SMILES: [C:1]1([CH:7]2[O:11][CH:10]([CH2:12][C:13]([OH:15])=[O:14])[C:9](=[C:16]=[CH2:17])[CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[K+].[K+].[C:24]1(I)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.O>CN(C)C=O.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]1([CH:7]2[O:11][CH:10]3[C:9]([C:16]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH2:17])([O:14][C:13](=[O:15])[CH2:12]3)[CH2:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: C=C=C1CC(c2ccccc2)OC1CC(=O)O
Reactant: Ic1ccccc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: C=C(c1ccccc1)C12CC(c3ccccc3)OC1CC(=O)O2
Temperature: 85 °C
Reaction time: 4 h

Procedure:
(5-phenyl-3-vinylidene-tetrahydro-furan-2-yl)acetic acid (32 mg, 0.12 mmol), Pd(PPh3)4 (14 mg, 0.012 mmol) and K2CO3 (84 mg, 0.61 mmol) were dissolved in 3 mL of dimethylformamide, followed by addition of PhI (68 μL, 0.61 mmol). The solution was stirred for 4 hours at 85° C. When the reaction was completed, H2O was added and the solution was stirred for 5 minutes. The mixture was diluted with ethyl acetate, washed with H2O and NaCl. Organic layer was separated and dried with anhydride MgSO4. Solvent was removed under reduced pressure, and the remnant was purified through silica gel tube chromatography (EtOAc:n-Hexane=1:15, v/v), thus providing products (26 mg, 62%).
Reaction SMILES: Br[C:2]1[C:3]2[CH2:10][CH2:9][CH:8]([NH:11][C:12](=[O:15])[CH2:13][CH3:14])[C:4]=2[CH:5]=[N:6][CH:7]=1.[F:16][C:17]1[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][C:18]=1B(O)O>>[F:16][C:17]1[CH:22]=[C:21]([C:23]([F:24])([F:25])[F:26])[CH:20]=[CH:19][C:18]=1[C:2]1[C:3]2[CH2:10][CH2:9][CH:8]([NH:11][C:12](=[O:15])[CH2:13][CH3:14])[C:4]=2[CH:5]=[N:6][CH:7]=1
Reactant: CCC(=O)NC1CCc2c(Br)cncc21
Reactant: OB(O)c1ccc(C(F)(F)F)cc1F
Product: CCC(=O)NC1CCc2c(-c3ccc(C(F)(F)F)cc3F)cncc21
Yield: 76 %

Procedure:
In analogy to the procedure described for the preparation of example 1, (rac)-N-(4-bromo-6,7-dihydro-5H-cyclopenta[c]pyridin-7-yl)propionamide (intermediate A-4) was reacted with 2-fluoro-4-(trifluoromethyl)phenylboronic acid to give the title compound as grey solid in 76% yield. MS: 353.1 (M+H+).
Reaction SMILES: [CH2:1]([Sn:5](CCCC)([C:12]1C=C[CH:15]=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4].[I:22]I>CO>[CH2:1]([Sn:5]([I:22])([CH2:12][CH2:13][CH2:14][CH3:15])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4]
Reactant: II
Reactant: CCCC[Sn](CCCC)(c1ccccc1)c1ccccc1
Solvent: CO
Product: CCCC[Sn](I)(CCCC)c1ccccc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
In a three-necked flask protected from light, dibutyl diphenyltin (10 g, 25.9 mmol) was solubilized in 50 mL of dry methanol. A solution of iodine (6.04 g, 23.76 mmol) in methanol was then added slowly. After stirring at room temperature for 16 hours, methanol was eliminated under vacuum. The residue was dissolved in petroleum ether and washed with a saturated aqueous solution of sodium thiosulphate. Organic layers were washed with a saturated sodium chloride solution and dried over MgSO4. Solvent was evaporated and the crude product was distilled using a Kugelrohr apparatus (rotating glass oven for fractionating distillation of small sample volumes at 60° C. A colourless oil was obtained (10.5 g, 24.0 mmol).
Reaction SMILES: C(Cl)(=O)C1C=CC=C(C(Cl)=O)C=1.[CH3:13][O:14][C:15](=[O:26])[C:16]1[CH:25]=[CH:24][CH:23]=[C:18]([C:19]([O:21]C)=[O:20])[CH:17]=1.O[Li].O>ClCCl.CO>[CH3:13][O:14][C:15](=[O:26])[C:16]1[CH:25]=[CH:24][CH:23]=[C:18]([C:19]([OH:21])=[O:20])[CH:17]=1
Reactant: COC(=O)c1cccc(C(=O)OC)c1
Agent: O=C(Cl)c1cccc(C(=O)Cl)c1
Agent: [Li]O
Solvent: ClCCl
Solvent: CO
Solvent: O
Product: COC(=O)c1cccc(C(=O)O)c1
Reaction time: 8 h

Procedure:
A solution of 12.18 g (60 mmol) isophthaloyl chloride in 60 ml dichloromethane was added to 60 ml anhydrous methanol at 0° C. The reaction was left overnight at rt. The reaction mixture was evaporated and the residue was dissolved in dichloromethane. The organic phase was washed twice with saturated NaHCO3 aq. The dichloromethane phase was dried and evaporated. Yield 11.05 g (56.9 mmol, 95%). A solution of 11.05 g (56.9 mmol) of isophthalic acid dimethyl ester and 2.39 g (56.9 mmol) LiOH.H2O in 150 ml anhydrous methanol was stirred for 4 d at rt The solvent was evaporated and the product was dissolved in water. The aqueous phase was washed with dichloromethane. The aqueous phase was made acidic with 2 M HCl aq. The product precipitated from the aqueous phase. The product was filtered off and dried in vacuo. The product was dissolved in 200 ml dry ethanol, and thereafter 600 ml water was added slowly while stirring. The product precipitated slowly overnight at +4° C. The product was filtered and dried in vacuo. Yield 8.32 g (46.2 mmol, 81%)
Reaction SMILES: C(OC([NH:11][C:12]1[CH:13]=[C:14]2[C:18](=[CH:19][CH:20]=1)[N:17](C(OCC1C=CC=CC=1)=O)[C@H:16]([CH3:31])[CH2:15]2)=O)C1C=CC=CC=1.[H][H]>C1COCC1.CO.[Pd]>[CH3:31][C@@H:16]1[CH2:15][C:14]2[C:18](=[CH:19][CH:20]=[C:12]([NH2:11])[CH:13]=2)[NH:17]1
Reactant: [H][H]
Reactant: C[C@@H]1Cc2cc(NC(=O)OCc3ccccc3)ccc2N1C(=O)OCc1ccccc1
Agent: [Pd]
Solvent: CO
Solvent: C1CCOC1
Product: C[C@@H]1Cc2cc(N)ccc2N1

Procedure:
A mixture of benzyl (2R)-5-{[(benzyloxy)carbonyl]amino}-2-methyl-2,3-dihydro-1H-indole-1-carboxylate (PCT/US00/08224; WO00/73301, 3.36 g, 8.07 mmol) and 10% palladium-on-carbon (108 mg) in THF/MeOH (1:1, 60 mL) is shaken on a Parr apparatus under a 36 psi hydrogen atmosphere overnight. The catalyst is removed by filtration through a pad of Celite, and the filtrate is concentrated under reduced pressure. Purification by chromatography on a Biotage Flash 40M 90 g silica gel cartridge (1-2% MeOH/CH2Cl2) affords the title compound, MS (ESI+) for C9H12N2 m/z 149 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH:17]=O)[CH:12]=2)[CH:3]=1.[CH3:19][N:20]([CH3:24])[CH2:21][CH2:22][NH2:23].C([BH3-])#N.[Na+].[C:29]([OH:36])(=[O:35])/[CH:30]=[CH:31]/[C:32]([OH:34])=[O:33]>C(O)(=O)C.CO>[C:29]([OH:36])(=[O:35])/[CH:30]=[CH:31]/[C:32]([OH:34])=[O:33].[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][NH:23][CH2:22][CH2:21][N:20]([CH3:24])[CH3:19])[CH:12]=2)[CH:3]=1
Reactant: CN(C)CCN
Reactant: N#Cc1ccc(Cl)cc1Oc1cccc(C=O)c1
Agent: O=C(O)/C=C/C(=O)O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: CN(C)CCNCc1cccc(Oc2cc(Cl)ccc2C#N)c1
Yield: 90.6 %

Procedure:
4-Chloro-2-(3-formylphenoxy)benzonitrile (0.20 g, 0.78 mmol), N,N-dimethylethylenediamine (90 μL, 72 mg, 0.82 mmol) and sodium cyanoborohydride (60 mg, 0.96 mmol) were stirred at ambient temperature in a 1% acetic acid/methanol solution (20 mL) for 5 days. The solvent was removed in vacuo. The residue was treated with 10% sodium carbonate solution and extracted with ethyl acetate. The ethyl acetate layer was separated and fumaric acid (0.10 g, 0.86 mmol) was added. After the solvent was removed in vacuo, the residue was triturated with ethyl acetate overnight, collected by filtration, and dried to give 4-chloro-2-{3-[(2-dimethylaminoethylamino)methyl]-phenoxy}benzonitrile fumarate (315 mg, 90%) as a white solid.
Reaction SMILES: [CH3:1][C:2]1([CH3:13])[C:6]2=[C:7]([OH:12])[CH:8]=[CH:9][C:10]([CH3:11])=[C:5]2[O:4][CH2:3]1.Cl[C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][N:16]=1.C([O-])([O-])=O.[K+].[K+]>CC#N.O.C(OCC)(=O)C>[N+:21]([C:18]1[CH:19]=[CH:20][C:15]([O:12][C:7]2[C:6]3[C:2]([CH3:13])([CH3:1])[CH2:3][O:4][C:5]=3[C:10]([CH3:11])=[CH:9][CH:8]=2)=[N:16][CH:17]=1)([O-:23])=[O:22]
Reactant: Cc1ccc(O)c2c1OCC2(C)C
Reactant: O=[N+]([O-])c1ccc(Cl)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CC#N
Product: Cc1ccc(Oc2ccc([N+](=O)[O-])cn2)c2c1OCC2(C)C
Temperature: 60 °C
Yield: 61.3 %

Procedure:
3,3,7-trimethyl-2,3-dihydro-1-benzofuran-4-ol (Intermediate 184, 0.9 g, 5.0 mmol) was dissolved in CH3CN (5 mL) in the presence of 2-chloro-5-nitropyridine (790 mg, 5.0 mmol) and K2CO3 (1.72 g, 12.5 mmol) and the resulting suspension was heated to 60° C. for 1.5 hrs. The mixture was then cooled to room temperature and diluted with water and ethyl acetate. Two phases were separated and the organic layer was washed with brine, then dried over Na2SO4 and evaporated to dryness, The residue was purified by flash chromatography on silica gel using cyclohexane to cyclohexane/ethyl acetate 90:10 as eluents affording the title compound (0.92 g) as yellowish solid.
Reaction SMILES: [CH3:1][C@@H:2]([C@@H:33]([OH:35])[CH3:34])[C@@H:3]1[O:5][C@H:4]1[CH2:6][C@@H:7]1[C@@H:12]([OH:13])[C@@H:11]([OH:14])[C@H:10]([CH2:15]/[C:16](/[CH3:32])=[CH:17]/[C:18]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([OH:31])=[O:30])=[O:19])[O:9][CH2:8]1.[Ca:36].C(C(CCCC)C([O-])=[O:41])C>C(OCC)(=O)C.O>[CH3:1][C@H:2]([C@H:3]1[C@H:4]([CH2:6][C@H:7]2[CH2:8][O:9][C@@H:10]([CH2:15]/[C:16](/[CH3:32])=[CH:17]/[C:18]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([O-:31])=[O:30])=[O:19])[C@H:11]([OH:14])[C@@H:12]2[OH:13])[O:5]1)[C@H:33]([CH3:34])[OH:35].[CH3:1][C@H:2]([C@H:3]1[C@H:4]([CH2:6][C@H:7]2[CH2:8][O:9][C@@H:10]([CH2:15]/[C:16](/[CH3:32])=[CH:17]/[C:18]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([O-:31])=[O:30])=[O:19])[C@H:11]([OH:14])[C@@H:12]2[OH:13])[O:5]1)[C@H:33]([CH3:34])[OH:35].[OH2:41].[OH2:5].[Ca+2:36]
Reactant: C/C(=C\C(=O)OCCCCCCCCC(=O)O)C[C@@H]1OC[C@H](C[C@@H]2O[C@H]2[C@@H](C)[C@H](C)O)[C@@H](O)[C@H]1O
Reactant: CCCCC(CC)C(=O)[O-]
Reactant: [Ca]
Solvent: O
Solvent: CCOC(C)=O
Product: C/C(=C\C(=O)OCCCCCCCCC(=O)[O-])C[C@@H]1OC[C@H](C[C@@H]2O[C@H]2[C@@H](C)[C@H](C)O)[C@@H](O)[C@H]1O
Product: [Ca+2]
Temperature: 5 °C
Reaction time: 14 h

Procedure:
Pseudomonic acid (10.00 g, 20 mmole) was dissolved in 100 ml of ethyl acetate at 40° C. Calcium-2-ethyl-hexanoate (3.32 g, 10 mmole) was suspended in 25 ml of water. The solution of pseudomonic acid was added to the calcium-2-ethyl-hexanoate suspension, and the resulting two phases system were stirred for 14 hours. The two phases were then separated, and any traces of ethyl acetate was evaporated from the aqueous phase. The aqueous mupirocin calcium suspension was cooled in the refrigerator to 5° C. and precipitated. The solid mupirocin calcium dihydrate was subsequently filtered, washed with 10 ml water and dried under vacuum at 35° C. for 14 hours. The mass of the product was 7.82 grams.
Reaction SMILES: Cl.[O:2]1[C:6]2[CH2:7][NH:8][CH2:9][CH2:10][C:5]=2[CH:4]=[CH:3]1.[CH:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:14]=[CH:13][C:12]=1[O:21][CH2:22][C:23](O)=[O:24].C(N(CC)CC)C.C(P(=O)(OCC)OCC)#N>ClCCl.O>[O:2]1[C:6]2[CH2:7][N:8]([C:23](=[O:24])[CH2:22][O:21][C:12]3[CH:13]=[CH:14][C:15]4[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=4)[CH:11]=3)[CH2:9][CH2:10][C:5]=2[CH:4]=[CH:3]1
Reactant: c1cc2c(o1)CNCC2
Reactant: O=C(O)COc1ccc2ccccc2c1
Agent: CCOP(=O)(C#N)OCC
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: O=C(COc1ccc2ccccc2c1)N1CCc2ccoc2C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 0.160 g (1.000 mmol) of 4,5,6,7-tetrahydrofuro[2,3-c]pyridine hydrochloride, 0.24 g (1.2 mmol) of 2-naphthoxyacetic acid and 0.55 ml (4.0 mmol) of triethylamine in 30 ml of dichloromethane, 0.24 g (1.5 mmol) of diethyl cyanophosphonate was added dropwise under ice-cooling, followed by overnight stirring at room temperature. The reaction mixture was poured into water and extracted with dichloromethane 2 times. The combined organic layer was washed with water and dried over anhydrous sodium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (hexane/ethyl acetate=3/1 to 1/1). The resulting product was purified by recrystallization from hexane/ethyl acetate (=1/1)-dichloromethane to yield the desired product.
Reaction SMILES: C(OC(=O)[NH:7][C@H:8]([CH2:24][C:25]1[CH:30]=[C:29]([F:31])[C:28]([F:32])=[CH:27][C:26]=1[F:33])[CH2:9][C:10](=[O:23])[N:11]1[CH2:17][C:16]2[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=2[NH:14][C:13](=[O:22])[CH2:12]1)(C)(C)C.[F:35][C:36]([F:41])([F:40])[C:37]([OH:39])=[O:38].CCCCCC>C(Cl)Cl>[F:35][C:36]([F:41])([F:40])[C:37]([OH:39])=[O:38].[NH2:7][C@H:8]([CH2:24][C:25]1[CH:30]=[C:29]([F:31])[C:28]([F:32])=[CH:27][C:26]=1[F:33])[CH2:9][C:10]([N:11]1[CH2:17][C:16]2[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=2[NH:14][C:13](=[O:22])[CH2:12]1)=[O:23]
Reactant: CC(C)(C)OC(=O)N[C@@H](CC(=O)N1CC(=O)Nc2ccccc2C1)Cc1cc(F)c(F)cc1F
Solvent: CCCCCC
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: N[C@@H](CC(=O)N1CC(=O)Nc2ccccc2C1)Cc1cc(F)c(F)cc1F
Temperature: 25 °C
Reaction time: 1 h
Yield: 73 %

Procedure:
To a solution of [(R)-3-oxo-3-(2-oxo-1,2,3,5-tetrahydro-benzo[e][1,4]diazepin-4-yl)-1-(2,4,5-trifluoro-benzyl)-propyl]-carbamic acid tert-butyl ester (40 mg, 0.08 mmol) in DCM (5 mL), was added trifluoroacetic acid (0.24 mL, 3 mL/mmol). The reaction mixture was stirred at r.t. for 1 h. After completion of the reaction, as confirmed by TLC, excess of trifluoroacetic acid and DCM were evaporated in vacuo to afford a gummy solid which was solidified from hexane to afford trifluoroacetic acid salt of 4-[(R)-3-amino-4-(2,4,5-trifluorophenyl)-butyryl]-1,3,4,5-tetrahydro-benzo[e][1,4]diazepin-2-one (30 Mg, 73%) as a solid.