D-Phenylalanine, methyl ester, hydrochloride (1:1)

White Solid

SYNTHESIS OF D-PHENYLALANINE METHYLESTER APPENDED NAPHTHALENEDIIMIDE (D-NDI or NDI 3B): SYNTHESIS OF D-PHENYLALANINE METHYLESTER HYDROCHLORIDE:Anhydrous methanol (50 mL) is taken in a 100 mL 2-necked round bottom flask fitted with a reflux condenser and an additional dropping funnel and cooled to ice temperature. Acetyl chloride (3 mL) is added drop wise through the dropping funnel. After 15 min, D-phenylalanine (3 g, 18.16 mmol) is added and the reaction mixture is refluxed at 70 °C for overnight. The reaction mixture is vacuo dried to obtain D- phenylalanine methylester hydrochloride in quantitative yield and used for further reaction without purification. 1, 4, 5, 8-naphthalenetetracarboxylic dianhydride (200 mg, 0.74 mmol) and D- phenylalanine methylester hydrochloride (322 mg 1.49 mmol) is suspended in DMF (20 mL) in a 100 mL round bottom flask. To this suspension triethylamine (0.6 mL) is added under inert atmosphere. The reaction mixture is refluxed at 75 °C for 24 h. Solvent is evaporated under vacuo and the residue is purified by column chromatography (1 percent methanol in chloroform). Yield 71percent. 107a. General procedure: For the synthesis of compounds 2a, 2c–2g, we used slightly modificated known procedure [1]. To a stirred solution of amino acid (32.2mmol) in dry methanol (100mL) was added drop-wise thionyl chloride (64.4mmol). The temperature was kept between−10 and−5°C. After complete addition, the reaction was stirred at RT overnight. After 16h, the solution was evaporated to dryness. The product was diluted with EtOAc and collected by filtration. The residue was dried under reduced pressure to give an amino acid methyl ester hydrochloride as white crystalline powder. The yields were higher in all experiments than 80percent. Melting point and General procedure: The methyl-esterification reaction of L-phenylalanine.To a suspension of L-phenylalanine (1 g, 6.05 mmol, 1.0 equiv) inmethanol (25 mL) cooled to 0 C was added thionyl chloride(475 mL, 6.66 mmol, 1.5 equiv) slowly. After 10 min, the reactionmixture was heated to 75 C to reflux for 2 h. After completion(monitored by TLC), the solvent was removed in vacuo, and at thistime, a white solid was formed methyl L-phenylalaninate hydrochloride(1.23 g, quantitative yield).D-Phenylalanine (1.3 g, 7.8 mmol) wasdissolved in dry MeOH and cooled to 0°C in an ice bath. Thionyl chloride (2.85 mL, 39.3 mmol) wasadded dropwise. The reaction mixture warmed to room temperature and stirred for 1 h. The solvent andreagent were removed under reduced pressure to yield the hydrochloride salt 8 as a white solid inquantitative yield. LRMS (ESI) m/z =180.3 [M+H]+.66.0 g (0.40 mol) of D-phenylalanine were suspended at room temperature in 400 ml of methanol in an anhydrous flask. Preparation of D-Phenylalanine methyl ester hydrochloride; Methanol (1200 mL) and D-phenylalanine (200 g) were taken in a round bottom flask at 25-30 General procedure: To a suspension of 5 g of D-amino acid in 100 mLdry methanol at 0–5°, 8–10 mL thionyl chloridewere added dropwise, the mixture was stirred for 2 hand kept at 20–22° for 24 h. The solvent was evaporatedunder vacuum at 30–40°, the residue wasmixed with dry ether, filtered off, dried, and recrystallizedfrom methanol–ether mixture.