Imidazole → (R)-Methyl 2-((tert-butoxycarbonyl)amino)-3-((tert-butyldimethylsilyl)oxy)propanoate

HRID 451777

Reaction equation

HRID 451777 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:14][OH:15])[C:10]([O:12][CH3:13])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CN=C1.[CH3:21][C:22]([Si:25](Cl)([CH3:27])[CH3:26])([CH3:24])[CH3:23]>CN(C=O)C>[CH3:21][C:22]([CH3:24])([Si:25]([CH3:27])([CH3:26])[O:15][CH2:14][C@H:9]([C:10]([O:12][CH3:13])=[O:11])[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH3:23]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 377723N-Boc-D-serine methyl ester

Product 1

HCID 10860583(R)-Methyl 2-((tert-butoxycarbonyl)amino)-3-((tert-butyldimethylsilyl)oxy)propanoateYield 95.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (R)-methyl 2-(tert-butoxycarbonylamino)-3-hydroxypropanoate (27.5 g, 0.126 mol) in DMF (250 mL) was added imidazole (25.7 g, 0.378 mol), followed by TBSCl (20.9 g, 0.139 mol) and the reaction mixture stirred for 4 h. The solvents were removed in vacuo and dissolved in EtOAc (300 mL). The solution was washed with saturated NH4Cl (2×100 mL), then with saturated NaHCO3 (100 mL), and brine (100 mL). The organic layer was then dried, filtered, and solvent removed in vacuo to give (R)-methyl 2,2,3,3,10,10-hexamethyl-8-oxo-4,9-dioxa-7-aza-3-silaundecane-6-carboxylate (40 g, yield 95%) as an oil that was used in the next step without further purification. 1H NMR (CDCl3, 400 MHz) δ 5.34 (brs, 1H), 4.35 (m, 1H), 4.05 (dd, J=13.2, 3.6 Hz, 1H), 3.82 (dd, J=14, 4.4 Hz, 1H), 1.45 (s, 9H), 3.73 (s, 3H), 0.86 (s, 9H), 0.02 (s, 6H).

Workup

  1. customThe solvents were removed in vacuo
  2. dissolutiondissolved in EtOAc (300 mL)
  3. washThe solution was washed with saturated NH4Cl (2×100 mL)
  4. customThe organic layer was then dried
  5. filtrationfiltered
  6. customsolvent removed in vacuo

Sources & evidence

ORD record
ord-b63ce11da3f74fe2a79c7e172c552d68
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Linked notes

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