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

HRID 406492Notes

Reaction equation

HRID 406492 reaction equation
[OH:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1.N1C=CN=C1.[C:23]([Si:27]([CH3:30])([CH3:29])Cl)([CH3:26])([CH3:25])[CH3:24]>CN(C=O)C>[Si:27]([O:1][C@H:2]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:11])([CH3:12])[CH3:13])=[O:8])[C@H:4]([C:14]([O:16][CH3:17])=[O:15])[CH2:3]1)([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:30])[CH3:29]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 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-dicarboxylateYield 72.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (2S,4R)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate (5.12 g, 20.8 mmol) in DMF (40 mL), imidazole (2.84 g, 41.7 mmol) and tert-butyldimethylchlorosilane (3.46 g, 22.9 mmol) were added sequentially and the mixture was stirred at ambient temperature for about 2 hours. The DMF was removed under reduced pressure and the residue partitioned between water (150 mL) and ether (150 mL). The organic phase was washed with 1N aqueous phosphoric acid (3×100 mL), water (2×100 mL), sodium bicarbonate saturated solution (2×100 mL) and brine (100 mL). The organic phase was dried with magnesium sulfate and concentrated to yield (2S,4R)-1-tert-butyl 2-methyl 4-(tert-butyldimethylsilyloxy)pyrrolidine-1,2-dicarboxylate (5.44 g, 15.1 mmol) as a colorless oil. RP-HPLC (Table 1, Method f) Rt 6.49 min.

Workup

  1. customThe DMF was removed under reduced pressure
  2. customthe residue partitioned between water (150 mL) and ether (150 mL)
  3. washThe organic phase was washed with 1N aqueous phosphoric acid (3×100 mL), water (2×100 mL), sodium bicarbonate saturated solution (2×100 mL) and brine (100 mL)
  4. dry with materialThe organic phase was dried with magnesium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-213b09cc5cb3423a95bbbab5c52785d7
Source dataset
uspto-grants-2014_06
Patent number
US08754107B2

Reaction notes

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