Boc-N-methyl-L-leucine

To a solution of Boc-L-Leu (5.0 g, 21.6mmol) in THF (73 mL) wasadded NaH (60percent dispersion in mineral oil, 10.0 g, 0.13 mol) inportions at 0 oC. After stirring at 0 oC for 30 min, MeI (4.1 mL, 66.0 mmol) and DMF (3.7 mL) were successively added. Thereaction was stirred for 30 min at 0 oC and additional 4 h atrt, until it was quenchedwith H2O (50 mL). The mixture was extracted by EtOAc (2×100 mL). The aqueoussolution was then acidified with 10percent aqueous KHSO4 solution to pH 5 and extractedwith ethyl acetate. The combined EtOAc extracts were washed with 5percent Na2S2O4solution and brine, and dried over Na2SO4, filtered and evaporated to give 13 (5.2 g, 98percent yield) as a colorless oil.General procedure: (S)-2-(Tert-butoxycarbonyl(methyl)amino)-3-hydroxypropanoic acid(6a) Gummy substance (This compound was prepared byadding neat sodium hydride (10 equiv.) in portion wiseover a period of 2.0 h to a cooled (0 °C) solution of (S)-2-(tert-butoxycarbonylamino)-3-hydroxypropanoic acid (1equiv.) and iodomethane (10 equiv.) in dry THF under astream of nitrogen. The reaction mixture was stirred at room temperature for 24 h under nitrogen atmosphere andthen diluted with ether (20 mL) and quenched with water(30 mL). The layers were separated and the aqueous layerwas extracted with ether (2 x9 15 mL), acidified to pH 3with a 20 percent aqueous solution of citric acid and extractedwith EtOAc (3 x 20 mL). The combined organic phasewas dried over Na2SO4 and evaporated to afford thecorresponding N-methylated product in 90 percent yield asGummy substance.)Boc—Leu—OH (4.7 g, 30 mmol) was dissolved in 150 mL of THF in an inert atmosphere. Sodium hydride (3.2 g, 133 mmol, 4.0 equiv.) was added at 0°C in portions. The reaction mixture was agitated 1 hour at low temperature before adding iodomethane (14.2 g, 100 mmol, 5.0 equiv.). The reaction was left under agitationovernight at ambient temperature and then neutralised with 100 mL of water and washed 3 times with 200 mL of EtOAc. The aqueous phase was brought to pH 3 with iN HC1 and then extracted 3 times with 100 mL of EtOAc. The organic phases were combined, washed once with 300 mL of NaC1—saturated aqueous solution, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure yielding 4.7g (94 percent) of compound 52A in the form of a red oil.

Molecular Weight:245.32
XLogP3:2.4
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:6
Exact Mass:245.16270821
Monoisotopic Mass:245.16270821
Topological Polar Surface Area:66.8
Heavy Atom Count:17
Complexity:281
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes