FMOC-SER-OME

White to off-white powder

To a mixed solution of a commercially available product of L-serine methyl ester hydrochloride (10.0 g, 64.3 mmol), 1, 4-dioxane (15 mL) and water (90 mL) was added sodium hydrogen carbonate (10.8 g, 129 mmol) at room temperature. The resultant mixture was stirred at room temperature for 15 minutes. Subsequently, a solution of 2, 5-dioxopyrrolidin-1-yl 9H-fluoren-9-ylmethylcarbonate (21.7 g 64.3 mmol) in 1, 4-dioxane (60 mL) was added to the resultant solution at room temperature, and the resultant mixture was stirred at room temperature for 14 hours. Water was added to the reaction mixture, the resultant solution was extracted with ethyl acetate three times, and a combined organic layer was washed with water and saturated brine. An organic layer was dried over anhydrous magnesium sulfate and then filtrated. The solvent was evaporated under a reduced pressure, diethyl ether and heptane were added to the resultant residue, and a precipitate was collected by filtration to give the title compound (22.3 g, yield: quantitative). Methyl 2S)-2-(((9H-fluoren-9-ylmethoxy)carbonyl)amino)-3-hydroxypropanoate To a solution of methyl L-serinate hydrochloride (1.00 g, 6.31 mmol, 1.00 equiv., RF1) in dioxane (5.00 mL, RR2) were added NaHCO3 (1.59 g, 18.9 mmol, 3.00 equiv, RR3) in H2O (25.2 mL, RR3) and Fmoc-OSu (2.55 g, 7.57 mmol, 1.20equiv, RR1) in dioxane (15.0 mL, RR1) diluted with dioxane (4.20 mL, RR4) andtransferred to RF1 at 25 °C. After being stirred at the same temperature for 5 h, the reaction mixture (RF1) was quenched with 1 M HCl aq. (RS2) and theaqueous layer was extracted with two portions of ethyl acetate (RS1). Thecombined organic layer was washed with 10percent NaCl aq. (RS3), dried overNa2SO4 (DT2), filtered, and concentrated in vacuo. The residue was purified bycolumn chromatography on silica gel (50percent ethyl acetate in hexane) to givemethyl (((9H-fluoren-9-yl)methoxy)carbonyl)-L-serinate (2.08 g, 6.09 mmol, 97percent) as a colorless oil.General procedure: Method A-using a planetary ball mill: The tritylated compound(1 mmol; typically 563 mg for 4) and In(OTf)3 (141 mg, 0.25 mmol)were allowed to mix in a stainless steel (SS) jar (capacity, 50 mL)containing SS balls (10 numbers, 10 mm o.d.) for 3.5 h (TLC, EtOAc:Hex, 1:1 for 4) in a planetary ball mill (PM-100) at550 rpm. EtOAc was added to the reaction mixture and the solutionwas transferred to a separatory funnel (50 ml 3). It was thenwashed successively with aq Na2CO3 solution (10percent, w/v, 50 ml 2)and water (50 ml), dried (Na2SO4), and concentrated underreduced pressure to afford the respective crude de-O-tritylated product. The crude product was purified by flash chromatography to free it from the by-product, TrOH (yield, 305 mg, 95.2percent, for 5from 4). It was crystallized from diethyl ether-n-Hex to obtain analytically pure product. The spectral data were in accordance with the expected structure and in agreement with the literature values. Method B—using a vibratory ball mill: The tritylated compound(1 mmol; typically 563 mg for 4) and In(OTf)3 (141 mg, 0.25 mmol)were allowed to mix in a SS jar (capacity, 10 mL) containing SSballs (20 numbers, 3 mm o.d.) for 15 min (TLC, EtOAc/Hex, 1:1 inthe case of 4) in a vibratory ball mill (MM-400) at 30 Hz. Theworkup and isolation of the product were carried out as describedin Method A above. Yield, 308 mg, 96.2percent for 5 from 4.To a suspension of 10 (263 mg, 0.80 mmol) inMeOH (5 mL) was added concentrated sulfuric acid (3 drops). After refluxing for 3 h, the mixture was cooled tort. The pH of the reaction mixture was then adjusted to 8 with an aqueous 20percent sodium carbonate solution, extracted with EtOAc. The organic layer was washed with brine, dried over MgSO4, and evaporated to give 11as a white solid (238 mg, 87percent). The spectral data of 11 were identical to the literature.34 The purity wasconfirmed by 1H NMR.

Molecular Weight:341.4
XLogP3:2.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:7
Exact Mass:341.12632271
Monoisotopic Mass:341.12632271
Topological Polar Surface Area:84.9
Heavy Atom Count:25
Complexity:460
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes