Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([Cl:10])[CH:9]=1)[CH2:5]Br.C([O-])([O-])=O.[K+].[K+].[C:17]([O:21][C:22]([NH:24][NH2:25])=[O:23])([CH3:20])([CH3:19])[CH3:18]>C(#N)C>[C:17]([O:21][C:22]([N:24]([CH2:5][C:4]1[CH:3]=[C:2]([Cl:1])[CH:9]=[C:8]([Cl:10])[CH:7]=1)[NH2:25])=[O:23])([CH3:20])([CH3:19])[CH3:18]
Reactant: CC(C)(C)OC(=O)NN
Reactant: Clc1cc(Cl)cc(CBr)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CC(C)(C)OC(=O)N(N)Cc1cc(Cl)cc(Cl)c1
Temperature: 25 °C
Yield: 52.7 %

Procedure:
3,5 Dichlorobenzyl bromide (10 g, 41.7 mmol) was dissolved in 200 mL of acetonitrile and K2CO3 (11.0 g, 83.36 mmol) and hydrazine carboxylic acid tert-butyl ester (11.0 g, 83.36 mmol) were added. The resulting mixture was warmed to reflux for 3 hours. The reaction mixture was then cooled to room temperature, concentrated in vacuo, and diluted with water and EtOAc. The aqueous phase was extracted with EtOAc, and the combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated to give a yellow oil. Purification by column chromatography (SiO2, 5–10% EtOAc/Hex eluent) provided 6.4 g of N-(3,5 dichlorobenzyl)hydrazine carboxylic acid tert-butyl ester as a white solid (53% yield). 1H NMR data is consistent with desired product. This material was dissolved in 200 mL of MeOH and SOCl2 (12.8 mL, 176.1 mmol) was added slowly. The resulting solution was stirred at room temperature for 5 hours and concentrated to give 5.8 g of 3,5-dichlorobenzyl hydrazine dihydrochloride salt as a pale yellow solid (100% yield). 66-2: E-2-tert-Butoxycarbonylamino-6-(methoxy-methylamino)-4-oxo-hex-5-enoic acid tert-butyl ester: Diprotected aspartic acid 66-1 (25 g, 86.41 mmol) and N,N-methoxymethylamine hydrochloride (8.85 g, 90.73 mmol) were dissolved in 180 mL of pyridine and this solution was cooled to 0° C. 1-[3-Dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDCI, 18.2 g, 95.05 mmol) was added in one portion and the resulting mixture was stirred at 0° C. for 90 minutes. The reaction mixture was then warmed to room temperature and stirred for another 90 minutes. The reaction mixture was diluted with EtOAC and 1N (aq) HCl solution. The organic phase was extracted with 1N (aq) HCl solution (3 times), concentrated, redissolved in EtOAc. This solution was extracted with 1N (aq) HCl solution (3 times) and once with brine, dried over Na2SO4, filtered and concentrated to give a yellow oil (28.81 g, >100% yield). 1H NMR is consistent with desired amide. A solution of ethynyl magnesium chloride (0.5 N in THF, 864 mL, 432 mmol) was cooled to −78° C. The amide prepared above was dissolved in 45 mL of THF and this solution was added via cannula to the cooled Grignard solution. The reaction mixture was then allowed to warm to room temperature and stirred overnight. The reaction mixture was then recooled to 0° C. and 1N (aq) HCl solution was added. The mixture was stirred at 0° C. for 30 minutes and then warmed to room temperature and stirred for 1 hour. EtOAc was then added and the organic phase was extracted with 1N (aq) HCl solution, water, and brine; dried over Na2SO4; filtered; and concentrated to give a brown oil. Purification by column chromatography (SiO2, 10–60% EtOAc in hexanes) provided about 10 g of a brown oil that solidified upon standing (ca. 33% yield). 1H NMR and LC/MS data are consistent with the desired product (66-2). 2D NMR techniques (HMQC, HMBC, and nOeSY) confirmed the structure as the E alkene. 66-3a: 2-tert-Butoxycarbonylamino-3-[2-(3,5-dichlorobenzyl)-2-H-pyrazol-3-yl]propionic acid tert-butyl ester: E-2-tert-Butoxycarbonylamino-6-(methoxy-methylamino)-4-oxo-hex-5-enoic acid tert-butyl ester (66-2, 3.54 g, 9.89 mmol) and pyridine (1.76 mL, 21.76 mmol) were combined in 100 mL of methanol. 3,5-Dichlorobenzyl hydrazine dihydrochloride (2.74 g, 10.38 mmol) was added and the resulting solution was stirred overnight at room temperature. The reaction mixture was concentrated to a brown oil. Purification by column chromatography (SiO2, 20% EtOAc in hexane as eluent) provided 2.25 g of a yellow oil (48% yield). 1H NMR spectrum is consistent with the desired product as the desired isomer (<10% of the 1,3 disubstituted pyrazole is present in this material). Another 140 mg of material was also isolated. This material corresponds to a 1:1 mixture of pyrazoles 66-3a : 66-3b as determined by 1H NMR. 66-4a: 2-Amino-3-[2-(3,5-dichlorobenzyl)-2-H-pyrazol-3-yl]propionic acid methyl ester (R=3,5 diClPh): 2-tert-Butoxycarbonylamino-3-[2-(3,5-dichlorobenzyl)-2-H-pyrazol-3-yl]propionic acid tert-butyl ester (66-3a, 2.25 g, 4.78 mmol) was dissolved in 50 mL of methanol and SOCl2 (2.8 mL, 38.26 mmol) was added slowly. The resulting solution was warmed to reflux for 18 hours, cooled to room temperature, and concentrated. The resulting brown foam was partitioned between EtOAc and saturated NaHCO3 solution. The aqueous phase was extracted with EtOAc. Combined organic phases were dried with Na2SO4, filtered and concentrated to give a brown oil (1.49 g, 95% yield). 1H NMR spectra is consistent with desired compound. 2-Amino-3-[2-(3,5-dichlorobenzyl)-2-H-pyrazol-3-yl]propionic acid methyl ester (66-4a, R=3,5 diClPh) was then alkylated with the triflate of leucic acid benzyl ester and the resulting diester was treated with aqueous NaOH solution in EtOH as previously described to proved the diacid 66-6 (R=3,5 diClPh). Equivalents