N,O-Di-BOC-D-tyrosine synthesis

Yield:1241677-97-3 100%

Reaction Conditions:

with sodium hydroxide in water;isopropyl alcohol at 37; pH=11.5 - 12;

Steps:

2 N,O-Bis(tert-butoxycarbonyl)-D-tyrosine. 3-2-1

W_fO-Bis(ferf-butoxycarbonyl)-D-tyrosine. 3-2-118,1g (100.0 mmol) D-tyrosine were suspended in 250 ml water and a solution of 65,4g (300.0 mmol) di-ieri-butyi dicarbonate in 150 mt 2-propanoi was added. The pH was adjusted to 11 ,5-12 by repeated addition of sodium hydroxide (32% in water). The reaction warmed slightly to about 37°C and was brought to 20°C by cooling. Then 250 ml water were added and the mixture extracted with ether. The combined organic phases were washed with water and dried over sodium sulfate. Evaporation of the soivent gave a gummy residue, which was taken up in ethyl acetate. The solution was filtered and hexane added. Upon evaporation, white crystals formed, which were dried i. vac. at 30°C. The yield was 39.1 g (>100%). a_D = -27.9 (c = 1 , dioxane).MS (ESf): m/e = 785 (2M + Na⁺), 763 (2M + H^?), 663 (2M + H⁺ - C₄H₈ - C0₂), 404 +).MS (ESP): m/e = 761 (2M - H⁺), 661 (2M - H⁺ - C₄H₈ - C0₂), 380 (M - H⁺).¹H NMR (DMSO-d₆ ,400MHz): δ (ppm) 7.25 (d, J=8.6 Hz, 2H, H-2'), 7.06 (d, J=8.6 Hz, 2H. H-3'), 6.88 (d, J=8.1 Hz, 1 H, NH), 4.03 (ddd, J=9.3, 8.3, 4.6 Hz, 1 H, H-2), 3.03 (dd, J=13.6, 4.5 Hz, 1 H, H-3), 2.83 (dd, J=13.6, 9.9 Hz, 1 H, H3), 1.48 (s, 9H), 1.32 (s, 9H). ¹³C NMR (DMSO-d₆ ,101 MHz): 6 (ppm) 173.4 (C-1 ), 155.3 (2C-1), 151.3 (4 -1 ), 149.1 (C-4'), 135.9 (C-1 '), 130.1 (C-2'), 120.9 (C-3'), 83.0 (4'C-2), 77.9 (2C-2), 55.3 (C-2), 35.9 (C-3), 28.1 (2C-3), 27.2 (4'C-3).

References:

WO2013/1088,2013,A1 Location in patent:Page/Page column 80-81