Reaction #1355742

Reaction equation

Citric acid

iodomethane

(2R)-3-Benzyloxy-2-tert-butoxycarbonylaminopropionic acid

tetrahydrofuran

sodium hydride

→

(2R)-3-benzyloxy-2-(tert-butoxycarbonylmethylamino)propionic acid

Conditions

Workup

1. 1
   OtherTetrahydrofuran was removed in vacuo
2. 2
   Extractionthe residue was extracted with methylene chloride (3×100 mL)
3. 3
   DryingThe organic phase was dried (magnesium sulfate)
4. 4
   Otherevaporated in vacuo
5. 5
   workup.DISSOLUTIONThe residue was dissolved in diethyl ether (20 mL)
6. 6
   workup.ADDITIONdicyclohexylamine (10 mL) and heptane (100 mL) were added
7. 7
   workup.WAITThe reaction mixture was left 3 days
8. 8
   workup.STIRRINGwithout stirring at 0° C
9. 9
   FiltrationThe reaction mixture was filtered

Procedure

(2R)-3-Benzyloxy-2-tert-butoxycarbonylaminopropionic acid (7.0 g; 23.7 mmol) was dissolved in dry tetrahydrofuran and iodomethane (11.9 mL; 189 mmol) was added. The reaction mixture was cooled to 0° C. and sodium hydride (60% in mineral oil) (2.73 g; 71 mmol) was added. The reaction mixture was left 3 days without stirring at 0° C. Citric acid (5%) was added until pH 2.5. Tetrahydrofuran was removed in vacuo and the residue was extracted with methylene chloride (3×100 mL). The organic phase was dried (magnesium sulfate) and evaporated in vacuo. The residue was dissolved in diethyl ether (20 mL) and dicyclohexylamine (10 mL) and heptane (100 mL) were added. The reaction mixture was left 3 days without stirring at 0° C. The reaction mixture was filtered to afford 5.78 g of (2R)-3-benzyloxy-2-(tert-butoxycarbonylmethylamino)propionic acid.

Source