Citric Acid → (2R)-3-benzyloxy-2-(tert-butoxycarbonylmethylamino)propionic acid
Reaction equation
[CH2:1]([O:8][CH2:9][C@@H:10]([NH:14][C:15](OC(C)(C)C)=O)[C:11]([OH:13])=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.IC.[H-].[Na+].C(O)(=O)[CH2:27][C:28]([CH2:33]C(O)=O)([C:30](O)=O)[OH:29].[O:39]1CCC[CH2:40]1>>[CH2:1]([O:8][CH2:9][C@@H:10]([NH:14][CH2:15][C:40]([O:29][C:28]([CH3:27])([CH3:30])[CH3:33])=[O:39])[C:11]([OH:13])=[O:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1Participants
Conditions
- Temperature
- 0 °C
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.
Workup
- customTetrahydrofuran was removed in vacuo
- extractionthe residue was extracted with methylene chloride (3×100 mL)
- dry with materialThe organic phase was dried (magnesium sulfate)
- customevaporated in vacuo
- dissolutionThe residue was dissolved in diethyl ether (20 mL)
- additiondicyclohexylamine (10 mL) and heptane (100 mL) were added
- waitThe reaction mixture was left 3 days
- stirringwithout stirring at 0° C
- filtrationThe reaction mixture was filtered
Sources & evidence
- ORD record
- ord-e9275af3b921425ba524860a41e8dd24
- Source dataset
- uspto-grants-1999_11
- Patent number
- US05977178
Reaction notes
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