Hydrochloric Acid → 3-Carboxytyrosine

Participants

Reaction Steps

A 250 mL 3-necked flask equipped with a magnetic stirrer and a condenser was charged with 4.1 g of 3-cyano-L-tyrosine and 100 mL of 6 N aqueous HCl. The mixture was heated to reflux with stirring. After 36 h, HPLC (C18, 90:10:0.1 H2O:MeCN:TFA) indicated no remaining starting material at k'=1.33 and a major new component at k'=1.69. The reaction mixture was cooled to RT, filtered to remove solids, and concentrated in vacuo to dryness. The residue was dissolved in 100 mL of 8:2 H2O:MeOH and the solution was passed through two C18 plugs (3.5×4.5 cm, EM separations LiChroprep RP-18) washing with 8:2 H2O:MeOH. The filtrate was concentrated in vacuo to dryness to afford 4.5 g of 3-carboxytyrosine as a brown solid. A portion of this material (1.30 g) was dissolved in 40 mL of 1,4-dioxane with 2 mL of concentrated H2SO4 and the solution was added to 30 mL of isobutylene (condensed at -78° C.) in a 300 mL pressure bottle equipped with a magnetic stirrer. The vessel was stoppered, warmed to RT and stirred. After 48 h, the bottle was cooled to 0° C. in an ice water bath, opened, and the mixture was treated with 20 g of NaHCO3. After allowing the isobutylene to evaporate, the mixture was suspended in 300 mL of water and extracted with CH2Cl2 (4×100 mL). The combined CH2Cl2 extracts were washed with 5% aqueous NaHCO2 (2×50 mL), dried over anhydrous MgSO4, and concentrated in vacuo to give a yellow-brown oil. Analysis by tlc (SiO2, 97:3 CH2Cl2 :MeOH) indicated a major component at Rf =0.41 and three minor components at Rf =0.30, 0.25 and 0.0. The crude material was purified by flash chromatography on 75 g of silica gel (94:6 CH2Cl2 :MeOH) to give 1.2 g of a light yellow oil. The oil was dissolved in 40 mL of ether and treated with 3.9 mL of 1 M ethereal HCl. A precipitate formed which was collected by filtration and dried in vacuo to afford 1.14 g (53%) of tert-butyl 3-(tert-butoxycarbonyl)-L-tyrosinate.HCl as a fluffy white solid. An analytical sample (26 mg) was prepared by recrystallization from MeOH-ether, m.p. 205° C. (dec). 1H-NHR: (300 MHz, DMSO-d6) δ 10.69 (s, 1 H, OH), 8.39 (br s, 3 H, NH3+), 7.57 (d, 1H, J=2.2, aromatic CH), 7.43 (dd; 1 H; J=8.6, 2.2; aromatic CH), 6.96 (d, 1 H, J=8.4, aromatic CH), 4.12 (m, 1 H, methine), 3.11 (dd; 1 H ; J=14.3, 5.3; ArCH2), 2.97 (dd; 1 H, J=14.1, 8.1; ArCH2), 1.57 (s, 9 H, t-Bu), 1.36 (s, 9 H, t-Bu).

Provenance & Evidence