D-p-Hydroxyphenylglycine

off-white powder

D-4-hydroxyphenylglycine is the D-enantiomer of 4-hydroxyphenylglycine. A non-proteinogenic amino acid found in Herpetosiphon aurantiacus. It is an enantiomer of a L-4-hydroxyphenylglycine. It is a tautomer of a D-4-hydroxyphenylglycine zwitterion.

Compound I-1 (31.0 mmol) was dissolved in 200 mL of a 1: 1 mixture of tetrahydrofuran and water, and Fmoc-Cl (32.5 mmol) and sodium bicarbonate (33.0 mmol) in 50 mL of tetrahydrofuran were added dropwise over 25 minutes. ). The mixed solution was stirred for 8 hours, then diluted with water and extracted with ether. The aqueous phase was acidified to pH = 3 and extracted with ethyl acetate. The combined organic layers were washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the organic solvent was removed by rotary evaporation under reduced pressure. The obtained crude product was recrystallized from ethyl acetate: petroleum ether (5: 1) to obtain a white solid, which is Compound I-2 (yield: 95%, Thionyl chloride (1.5mL, 33.0mmol) was added dropwise to a suspension of (R)-4-hydroxyphenylglycine 15 (5.00g, 29.91mmol) in dry methanol (25mL) while stirring at 15°C under nitrogen. The reaction mixture was allowed to warm to room temperature and stirred overnight. The yellow solution was then brought to reflux for 30min. The reaction mixture was concentrated under reduced pressure to give the hydrochloride salt 16 as an off-white solid. The hydrochloride salt 16 was stirred in diethyl ether (15mL), filtered and washed with diethyl ether (2×15mL) and dried to give the hydrochloride salt 16 (6.50g, 100percent) as a white solid, mp 189-191°C; [alpha]20D=?120.9[alpha]D20=-120.9 (c 1, 1M HCl), {Lit., 34 [alpha]25D=?121.1[alpha]D25=-121.1 (c 1, 1M HCl)}; numax/cm1 (KBr) 3339 br, 1740 (CO), 1595; deltaH (300MHz, DMSO-d6) 3.68 (3H, s, OCH3), 5.11 [1H, s, C(2)H], 6.80 (2H, d, J 8.5, aromatic H), 7.25 (2H, d, J 8.5, aromatic H), 8.70 (3H, br s, NH3), 9.86 (1H, s, OH).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).A slurry of (D)-4-hydroxyphenyl glycine 1 (10 mmol) in methanol (100 mL) is stirred with cooling in an ice bath. Thionyl chloride (11 mmol) is added dropwise over the course of 15 minutes. After addition is complete, the mixture is allowed to stir in the cooling bath for an additional 2 hours. The mixture is then concentrated to dryness to afford crude (D)-4-hydroxyphenyl glycine methyl ester hydrochloride. A slurry of (D)-4-hydroxyphenyl glycine 1 (10 mmol) in methanol (100 mL) is stirred with cooling in an ice bath. Thionyl chloride (11 mmol) is added dropwise over the course of 15 minutes. After addition is complete, the mixture is allowed to stir in the cooling bath for an additional 2 hours. The mixture is then concentrated to dryness to afford crude (D)-4-hydroxyphenyl glycine methyl ester hydrochloride. This material is dissolved and stirred in 100 mL dimethylformamide and treated sequentially with diisopropylethyl amine (22 mmol) followed by allyl 1-benzotriazolyl carbonate (11 mmol). After stirring I hour at room temperature, volatiles are removed under reduced pressure and the residue is fractionated by silica gel chromatography using ethyl acetate/hexane eluent to afford Aloc-protected (D)-4-hydroxyphenyl glycine methyl ester. The ester (7.0 mmol) is dissolved in methanol (40 mL, stirred at room temperature, and treated with a solution of lithium hydroxide (8.0 mmol) in 20 mL water. The reaction is stirred at room temperature for 2 hours and then poured into 100 mL 1 N sodium hydrogen sulfate solution and extracted with ethyl acetate. The organic extract is dried over anhydrous sodium sulfate, filtered, and then concentrated under reduced pressure. The crude is fractionated via chromatography on silica gel using methanol/methylene chloride/trifluoracetic acid eluent to afford N-Aloc (D)-4-hydroxyphenyl glycine 14.To a stirred solution of 4-hydroxy-(Z))-phenylglycine (50.0 g, 0.299 mol) in methanol (500 mL) was added thionyl chloride (32.66 mL, 0.499 mol) at 0-5 °C. The mixture was then allowed to stir overnight at room temperature. Reaction mixture was concentrated under reduced pressure at 50 °C to get hydrochloride salt of ( ?)-amino-(4-hydroxyphenyl)acetic acid methyl ester. To the above obtained compound (40.0 g, 0.184 mol) was added tetrahydrofuran (400.0 mL) and triethylamine (56.3 mL, 0.404 mol), followed by 9- fluorenmethylsuccimidyl carbonate (68.2 g, 0.202 mol) at 0-5 °C. The mixture was then stirred at room temperature for 2 hours. Reaction mixture was concentrated under reduced pressure at 35 °C to get crude which was purified by column chromatography (silica gel 230- 400 mesh, ethyl acetate: n-hexane, 50: 50) to get ( ?)-[(9H-fluoren-9- ylmethoxycarbonylamino)]-(4-hydroxyphenyl)acetic acid methyl ester.Step 1:To a solution of (R)-2-amino-2-(4-hydroxyphenyl)acetic acid 25a(D-4Hydroxyphenyl glycine, 10.0 g, 60.1 mmol) in methanol (200 mL) was added dropwise thionyl chloride (8 mL) and stirred at room temperature for 10 h. The reaction mixture was concentrated in vacuum and the residue was washed twice with ether to yield (Pv)-methyl 2-amino-2-(4-hydroxyphenyl)acetate (To 50 mL of methanol cooled to 0C was dropwise added 3.75 mL of thionyl chloride foolowed by 5.0g (0.030 mmol) of : Synthesis of D-HPGM in crystal form i) Synthesis o. D-HPGM from D-HPG A reactor was loaded with 7 moles of methanol (0.1 % v/v H20), 1 .2 moles of sulphuric acid (H2S04 98%) and 1 mol of HPG (ee >99.8%) (step a). The reaction mixture was heated until reflux to a temperature of about 74C and the reaction mixture was stirred during 2 hours (step b). Subsequently, water which was formed during the reaction under b) and the remaining methanol were distilled off under vacuum in batch at ynthesis of Methyl (2R)-Amino(4-Hydroxyphenyl)EthanoateTo a solution of (2J?)-amino(4-hydroxyphenyl)ethanoic acid (1 g, 5.98 mmol) in dry methanol (50 ml) was added thionyl chloride (1.05 ml, 154.97 mmol) drop- wise at 0C. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under vacuum, basified with a saturated solution of sodium bicarbonate (pH~9) and extracted with ethyl acetate. The combined ethyl acetate layers were washed with water, dried over anhydrous sodium sulphate, filtered and the solvent evaporated off under vacuum to afford the title compound as light brown oil. This compound was used as such for the next step without purification. Yield: 1 g.(R)-2-amino-2-(4-hydroxyphenyl)acetic acid (7.10 g, 42.5 mmol) was dissolved in methanol (85 mL), stirred for 10 min in an ice bath, and thionyl chloride (3.72 mL, 51.0 mmol) was slowly added thereto. The resulting mixture was reflu ed under a nitrogen atmosphere for 2 hrs, followed by cooling down to room temperature. The reaction solution was concentrated under reduced pressure and the residue obtained was used in the next step without further purification. 1H NMR (600MHz, DMSO-d6) delta 2.18 (2H, br), 3.53 (3H, s), 4.36 (1H, s), 6.66 (2H, d), 7.12 (2H, d), 9.33 (1H, s)To a solution of (R)-2-amino-2-(4-hydroxyphenyl)acetic acid (1.0 g, 6.0 mmol) in MeOH (10 mL) was added SOC12 (1.3 ml, 18.0 mmol) dropwise. The mixture was stirred at RT for 0.5 h. The mixture was concentrated to give the crude product of the title compound methyl (R)-2-amino-2-(4-hydroxyphenyl)acetate (2-3a). MS-ESI (m/z): 182 [M + 1].

4-Hydroxy-D-(-)-2-phenylglycine is an compound used mainly for the synthetic preparation of β-lactam antibiotics.

Molecular Weight:167.16
XLogP3:-2.1
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:167.058243149
Monoisotopic Mass:167.058243149
Topological Polar Surface Area:83.6
Heavy Atom Count:12
Complexity:164
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes