Imidazole → (2S,4R)-1-tert-Butyl 2-methyl 4-((tert-butyldimethylsilyl)oxy)pyrrolidine-1,2-dicarboxylate

HRID 1672389Notes

Reaction equation

HRID 1672389 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([OH:13])[CH2:10][C@H:9]1[C:14]([O:16][CH3:17])=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C=O)C.N1C=CN=C1.[Si:28](Cl)([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29]>CCOCC>[Si:28]([O:13][C@H:11]1[CH2:12][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[C@H:9]([C:14]([O:16][CH3:17])=[O:15])[CH2:10]1)([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 6228DimethylformamideHCID 28928tert-Butyldimethylsilyl chlorideHCID 2734883(2S,4R)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

Product 1

HCID 10618477(2S,4R)-1-tert-Butyl 2-methyl 4-((tert-butyldimethylsilyl)oxy)pyrrolidine-1,2-dicarboxylate

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

Methyl (2S,4R)—N-tert-butoxycarbonyl-4-hydroxy-2-pyrrolidinecarboxylate (5.00 g, 0.0198 mol) was dissolved in anhydrous DMF (30 mL, 0.4 mol) under an atmosphere of nitrogen. To this solution was added 1H-imidazole (3.2 g, 0.046 mol) followed by tert-butyldimethylsilyl chloride (3.92 g, 0.0260 mol). The resulting mixture became translucent. After stirring for 16 h at RT, the reaction mixture was diluted with ether (100 mL) and washed with water (3×20 mL), and brine (2×10 mL), then dried (Na2SO4), filtered, concentrated and purified by CombiFlash chromatography (120 g column, eluting with 0-25% EtOAc/hexanes). LC/MS: 260.2 (M−Boc+2H).

Workup

  1. washwashed with water (3×20 mL), and brine (2×10 mL)
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by CombiFlash chromatography (120 g column, eluting with 0-25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-83eb35854e984ee4b50b2516d8772f52
Source dataset
uspto-grants-2011_08
Patent number
US07998959B2

Reaction notes

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