L-Tyrosine, methyl ester, hydrochloride

Crystalline

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).The L- tyrosine (110g, 0.607mol) was added to 500mL of methanol, cooled to 0 deg.] C, was added dropwise thionyl chloride (108.3g, 0.91mol). After the dropwise addition to naturally warm to room temperature and then the reaction was heated at reflux for 5h, TLC monitored the reaction was complete. It cooled to room temperature, filtered, the filter cake washed with 420mL of ethyl acetate with drying of 140.2 g of a white solid, a yield of 99.7percent.In an ice bath, acetyl chloride (21.32 mL, 300 mmol) was added into 200 mL anhydrous methanol slowly. After stirred for 30 min, L-tyrosine (18.1 g, 100 mmol) was added into the solution. Then the solution was reuxed for 4 h in an oil bath and the solvent was removed under reduced pressure. The residue was added some acetone and filtered to give 22.78 g of L-tyrosine methyl ester hydrochloride as a white powder, yield: 99percent. Di-tert-butyl dicarbonate (11.34 g, 52 mmol) in 50 mL 1, 4-dioxane was slowly added into the solution of L-tyrosine methyl ester hydrochloride (9.26 g, 40 mmol), K2CO3 (8.28 g, 60 mmol) in 160 mL mixture solvent (1, 4-dioxane–H2O = 1:1). After stirred overnight at room temperature, the reaction mixture was concentrated under reduced pressure and EtOAc was added. The EtOAc layer was washed by 1 N citric acid, saturated NaHCO3 and brine. The organic layer was dried over anhydrous MgSO4 and concentrated to give compound 2 as a white powder. It could be directly used in the further steps without purication.Step A. Synthesis of L-p-tyrosine-methyl ester hydrochloride (2) and various isomers of (2) (D-p-tyr, DL-σ-tyr, L-m-fyr))[0094] A solution of tyrosine 1 (D-p-, DL-o-, L-m- or L-p-, 1.67 mmol) in anhydrous methanol was stirred at 0Thionyl chloride (10 mL, 139 mmol) was added drop-wise to a stirred solution of L-tyrosine (10.0 g, 55.25 mmol) in dry MeOH (100 mL) at 0 C and the reaction mixture was stirred at ambient temperature for 24 h. Volatiles were removed under diminished pressure to afford L-tyrosine methyl ester hydrochloride (IUPAC name: methyl (2S)-2-amino-3-(4-hydroxyphenyl)propanoate hydrochloride) as a white solid (11.73 g, 91.6 percent yield). 1H NMR (400 MHz, DMSO-d6), δ: 9.49 (brs, 1H), 8.66 (brs, 3H), 7.0 (d, J = 8.4 Hz, 2H), 6.76–6.68 (m, 2H), 4.19–4.06 (m, 1H), 3.65 (s, 3H), 3.11 (dd, J = 14.1 Hz, J = 5.7 Hz, 1H), 3.02–2.95 (dd, J = 14.1 Hz, J = 7.1, 1H). 13C NMR (100 MHz, DMSO-d6), δ: 35.08, 52.51, 53.47, 115.43, 124.34, 130.36, 156.70, 169.44.SOCl2 (906 mL, 12.5 mmol) was added to anhydrous MeOH (18mL) in an ice-water bath. After 30 min, L-tyrosine (0.906 g, 5.00mmol) was added, and the mixture was stirred at room temperaturefor 36 h. After removal of the solvent, the residue was purifiedby silica gel chromatography (CHCl3:MeOH = 14:1'12:1'5:1'0:1) to afford L-tyrosine methyl ester hydrochloride (b, 0.876g, 90percent) as a white powder(2S)-3-(4-hydroxyphenyl)-1-methoxy-1-oxopropan-2-aminium chlorideThionyl chloride (6.62 mmol, 0.48 mL) was added dropwise to a solution of L- tyrosine (0.600 g, 3.31 mmol) in methanol (22 mL). The reaction was heated to reflux with vigorous stirring for 24 h. After cooling, the reaction mixture was concentrated under reduced pressure and the residual methanol removed by azeotropic distillation with dichloromethane (10 mL) under reduced pressure to give the title compound as a white solid (0.646 g, 84percent).*H NMR (500 MHz, DThionyl chloride (6.62 mmol, 0.48 mL) was added dropwise to a solution of L-tyrosine (0.600 g, 3.31 mmol) in methanol (22 mL). The reaction was heated to reflux with vigorous stirring for 24 h. After cooling, the reaction mixture was concentrated under reduced pressure and the residual methanol removed by azeotropic distillation with dichloromethane (10 mL) under reduced pressure to give the title compound as a white solid (0.646 g, 84percent). [0422] General procedure: Compounds 6–8 were synthesized using the following general procedure reported by Maiti and Banerjee [50]: a solution of amino acid (18.2mmol) in MeOH (20mL) was stirred at 0°C. Thionyl chloride (1.6mL, 22mmol) was added dropwise over 10min. The reaction mixture was then allowed to warm to room temperature before being heated under reflux for 3h. The solvent and volatiles were evaporated under reduced pressure and the product was triturated with ethyl acetate to give the methyl ester hydrochloride salt as a colorless solid (100percent). General procedure: A mixture of the corresponding acid precursor (1 eq) in MeOH (12 mL) was added SOCl2 (1.3 eq) dropwise at 0 C. The resulting solution was heated at 75 C for 21 h. On cooling, the mixture was concentrated to give the expected product.

Molecular Weight:231.67
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:4
Exact Mass:231.0662210
Monoisotopic Mass:231.0662210
Topological Polar Surface Area:72.6
Heavy Atom Count:15
Complexity:188
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:2
Compound Is Canonicalized:Yes