α-[[(1,1-DiMethylethoxy)carbonyl]aMino]-2-fluoro-4-hydroxybenzeneacetic Acid synthesis

Yield:-

Reaction Conditions:

Stage #1:amino-(2-fluoro-4-hydroxyphenyl)acetic acid hydrochloride;di-tert-butyl dicarbonate with sodium carbonate in 1,4-dioxane;water at 20; for 2.7 h;
Stage #2: with hydrogenchloride;water in 1,4-dioxane;ethyl acetate

Steps:

102
Preparation 102: ferf-Butoxycarbonylamino-(2-fluoro-4-hydroxyphenyl)acetic acid; A solution of Na₂CO₃ (1.89 g, 17.8 mmol) in H₂O (25 mL) was added to a suspension of amino-(2-fluoro-4-hydroxyphenyl)acetic acid hydrochloride (Preparation 101, 2.40 g, 8.90 mmol) in dioxane (50 mL) and the resulting reaction mixture was stirred at ambient temperature for 2 min before the addition of di-ferf-butyldicarbonate (2.14 g, 9.80 mmol). The reaction mixture was stirred at ambient temperature for 4 h, then EtOAc (100 mL) and IM HCl (100 mL) were added. The aqueous phase was extracted with EtOAc and the combined organics were washed with IM HCl (50 mL) and brine (50 mL), dried (MgSO₄), filtered and concentrated in vacuo to afford the title compound: RT = 2.76 min, m/z (ES⁺) = 571.2 [2M + H]⁺.

References:

PROSIDION LIMITED WO2009/34388, 2009, A1 Location in patent:Page/Page column 55-56