PHT-ALA-OH

White crystals

To a stirred solution of 2 in H2O (100 mL) were added L-alanine(8.9 g, 100.00 mmol) and Na2CO3 (10.6 g, 100.00 mmol). After1.5 h, the aqueous solution was slowly acidified with aqueousHCl (1 N) until pH = 1–2, and filtered to obtain 17.37 g (79.3percent yield)as white solid. Mp 145.8–146.6 C. 1H NMR (CDCl3, 400 MHz) d1.71 (s, 3H, CH3), 5.02 (q, J = 7.4 Hz, 1H, CH), 7.69–7.75 (m, 2H, Ar-H), 7.82–7.88 (m, 2H, Ar-H). MS (ESI): m/z 218.2 [MH].II-1 the compound (21.9g, 100mmol) and L-alanine (8.9g, 100mmol) dissolved in HGeneral procedure: The synthesis of 2-imidoalkanecarboxylic acids 6 wascarried out based on the modified procedure described byMcKenzie and Walker [32]. The corresponding α-amino acid(10 mmol) was heated with phthalic or succinic anhydride(11 mmol) at 170 °C or 140 °C under reduced pressure for thetime given in Table 1. The crude product was recrystallizedfrom toluene.Example 14Preparation of (1R, 2S)-1-phenyl-2-(4-(2-methoxyphenyl)piperazinyl)propan-1-ol (II-1) hydrochloride and (1S, 2S)-1-phenyl-2-(4-(2-methoxyphenyl)piperazinyl)propan-1-ol (II-2) hydrochloride1) Preparation of (S)-2-(1, 3-dicarbonyl isoindole) propionic acid(S)-2-amino propionic acid (4.45 g, 0.05 mol), phthalic anhydride (7.40 g, 0.05 mol) and triethylamine (0.8 ml) were added to 150 ml of toluene, and heated till refluxing. A reaction was allowed to proceed for 24 hours. The reaction mixture was cooled, evaporated to remove the solvent, added to 50 ml of water, and extracted with ethyl acetate (3.x.50 ml). The ethyl acetate layer was washed with saturated brine, dried with anhydrous sodium sulfate, filtered, and evaporated to remove the solvent, thereby obtaining 9.9 g of white solid. The yield was 90.3percent.MS: m/z 219.1.The brown residue obtained from the above procedure was mixed with 105 phthalic anhydride (5.5 mmol), 106 triethylamine (5.5 mmol) and 13 toluene (50 mL). The mixture was refluxed overnight in a round bottom flask equipped with a Dean-Stark trap. The reaction was cooled to r.t. and the mixture was concentrated in vacuum to give the crude product, which was then dissolved in 107 dichloromethane (DCM). To the 108 DCM solution was added a 109 concentrated aqueous HCl solution (37percent, 1 mL). The mixture was washed with water and the organic layer was dried over NaGeneral procedure: The (S)-amino acids 1a–c and 1e (1mmol, 1equiv) and phthalic anhydride (1.5mmol, 1.5equiv) were heated together at 130–160°C. After completion of the reaction, the unreacted phthalic anhydride was scraped off from the walls of the flask and the crude acid that remained in the flask was purified by crystallization, from different solvents, to afford pure crystals of 3a–c, e (Table 4). 4.1.1 General procedure: A 20mL PFR was constructed by coiling 81.5m of 1.59mm OD (0.56mm ID) stainless steel tubing. The PFR was placed in a gas chromatography oven that was modified for use as a PFR thermostat. 2.07MPa back pressure was provided by an Equilibar® backpressure regulator connected to a nitrogen cylinder. After depressurization, the product stream was collected in a glass pressure bottle under an atmosphere of nitrogen. The feed solution was pumped using an Isco® 1000D high pressure syringe pump and the flow rate was not calibrated. 100.0 g of ester 3a (estimated at 92.7percent w/w, 92.7g, 0.461mol) was dissolved in 1500 mL of 1:1 (v/v) 2-propanol : water and ~1000mL of this solution was charged to the syringe pump. The reactor was filled with 1:1 (v/v) 2-propanol:water solvent. The oven temperature was set to 160 °C and when the temperature had stabilized, flow from the reagent pump was initiated at 0.847mL/min (V/Q=23.61min). During the start up phase, samples were collected from the stream immediately after the reactor prior to the back pressure regulator in order to characterize the transition curve using

Molecular Weight:219.19
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:219.05315777
Monoisotopic Mass:219.05315777
Topological Polar Surface Area:74.7
Heavy Atom Count:16
Complexity:328
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes