Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:3]([Cl:13])=[C:4]([CH:8]=[C:9]([F:12])[C:10]=1[CH3:11])[C:5]([OH:7])=[O:6].CO.Cl.[C:17](=O)([O-])[O-].[Na+].[Na+]>O>[NH2:1][C:2]1[C:3]([Cl:13])=[C:4]([CH:8]=[C:9]([F:12])[C:10]=1[CH3:11])[C:5]([O:7][CH3:17])=[O:6]
Reactant: O=C([O-])[O-]
Reactant: Cc1c(F)cc(C(=O)O)c(Cl)c1N
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COC(=O)c1cc(F)c(C)c(N)c1Cl

Procedure:
12 g of 3-amino-2-chloro-5-fluoro-4-methylbenzoic acid are initially introduced into 60 ml of MeOH. HCl gas is passed in for 20 minutes and is then boiled under reflux for 5 hours. Thereafter, the mixture is poured into water and rendered alkaline with sodium carbonate and the product is isolated. Yield: 8 g, melting point: 51°-52°.
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH2:22][C@H:21]1[CH2:25]O)=[O:19])([CH3:16])([CH3:15])[CH3:14].[I:27]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH2:22][C@H:21]1[CH2:25][I:27])=[O:19])([CH3:16])([CH3:15])[CH3:14]
Reactant: II
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1CO
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC[C@H]1CI
Temperature: 25 °C
Yield: 76.2 %

Procedure:
Under a nitrogen atmosphere, a solution of diethyl azodicarboxylate (4.699 g, 26.98 mmol) in dry tetrahydrofuran (THF) (15 mL) was added drop-wise to an ice-cold stirring solution of (2S)-N-(tert-butoxycarbonyl)-2-(hydroxymethyl)pyrrolidine (5.37 g, 26.7 mmol), iodine (3.42 g, 13.5 mmol) and triphenylphosphine (7.069 g, 26.95 mmol) in dry THF (50 mL). The mixture was stirred and allowed to warm to ambient temperature overnight. The mixture was concentrated on a rotary evaporator and then the residue was stirred with 5% aqueous Na2S2O3 (50 mL). After stirring for 30 min, the mixture was extracted with dichloromethane (4×25 mL). The combined dichloromethane extracts were dried (Na2SO4), filtered and concentrated. The residue was repeatedly crystallized (three to four times) from dry ether and finally from heptane to give 3.20 g (38.6%) of product.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:16])[CH:5]([CH2:9][NH:10][CH:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1)[CH2:6][CH2:7][CH3:8])[CH3:2].[Cl:17][C:18]1[N:23]=[C:22](Cl)[C:21]([N+:25]([O-:27])=[O:26])=[CH:20][N:19]=1.C(=O)(O)[O-].[K+]>O.C(OCC)C>[CH2:1]([O:3][C:4](=[O:16])[CH:5]([CH2:9][N:10]([C:20]1[C:21]([N+:25]([O-:27])=[O:26])=[CH:22][N:23]=[C:18]([Cl:17])[N:19]=1)[CH:11]1[CH2:12][CH2:13][CH2:14][CH2:15]1)[CH2:6][CH2:7][CH3:8])[CH3:2]
Reactant: CCCC(CNC1CCCC1)C(=O)OCC
Reactant: O=[N+]([O-])c1cnc(Cl)nc1Cl
Agent: O=C([O-])O
Agent: [K+]
Solvent: O
Solvent: CCOCC
Product: CCCC(CN(c1nc(Cl)ncc1[N+](=O)[O-])C1CCCC1)C(=O)OCC
Temperature: 25 °C
Reaction time: 3 h
Yield: 72.8 %

Procedure:
A solution of 1.14 g (0.005 mole) of (rac)-2-cyclopentylaminomethyl-pentanoic acid ethyl ester in 25 mL of water was added dropwise to a solution of 0.97 g (0.005 mole) of 2,4-dichloro-5-nitro-pyrimidine in 25 mL of ethyl ether. At 0 degrees, 1.0 g (0.010 mole) of potassium bicarbonate was added. The mixture was stirred at ambient temperature for 3 hours. The layers were then separated, and the aqueous layer extracted twice with 30 mL of ether. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography, eluting with hexanes-ethyl acetate (100:0-80:20) gave 1.4 g of (rac)-2-{[(2-chloro-5-nitro-pyrimidin-4-yl)-cyclopentyl-amino]-methyl}-pentanoic acid ethyl ester (IV-16).