Tert-butyl acetoacetate → 2-(2-Tert-butoxycarbonyl-3-oxo-butyryl)-pyrrolidine-1-carboxylic acid benzyl ester

HRID 1170470Notes

Reaction equation

HRID 1170470 reaction equation
[C:1]([O:5][C:6](=[O:11])[CH2:7][C:8]([CH3:10])=[O:9])([CH3:4])([CH3:3])[CH3:2].C[Mg]Cl.[CH2:15]([O:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][CH:26]1[C:30](Cl)=[O:31])=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1COCC1>[CH2:15]([O:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][CH:26]1[C:30](=[O:31])[CH:7]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:11])[C:8](=[O:9])[CH3:10])=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 15538Tert-butyl acetoacetateHCID 98601531-Pyrrolidinecarboxylic acid, 2-(chlorocarbonyl)-, phenylmethyl esterHCID 178418332HCID 178418332, compound

Product 1

HCID 598504652-(2-Tert-butoxycarbonyl-3-oxo-butyryl)-pyrrolidine-1-carboxylic acid benzyl esterYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of tert-butylacetoacetate (7.90 g, 50.0 mmol) in anhydrous THF (50 mL) was cooled to 4° C. (ice-water bath) prior to dropwise addition of methylmagnesium chloride (16.3 mL of a 3.00M solution in THF, 50.0 mmol) at such a rate that the temperature did not exceed 10° C. After the addition was complete the cooling bath was removed. When the temperature reached 15° C., 2-chlorocarbonyl-pyrrolidine-1-carboxylic acid benzyl ester (6.60 g, 25.0 mmol) was added dropwise over 1 h then warmed to rt and stirred for 12 h. The reaction was quenched with saturated aqueous NH4Cl (30 mL). The organic layer was separated from the solid residues and concentrated under vacuum to give 9.74 g (quant.) of 2-(2-tert-butoxycarbonyl-3-oxo-butyryl)-pyrrolidine-1-carboxylic acid benzyl ester as a yellow oil. The product was used directly in the subsequent step without further purification.

Workup

  1. customdid not exceed 10° C
  2. additionAfter the addition
  3. customwas removed
  4. customreached 15° C.
  5. customThe reaction was quenched with saturated aqueous NH4Cl (30 mL)
  6. customThe organic layer was separated from the solid residues
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-848d797c46a94a32bba32ddb90ca2649
Source dataset
uspto-grants-2010_11
Patent number
US07825256B2

Reaction notes

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