Glycine tert-butyl ester → 5-[(Tert-butoxycarbonylmethyl-amino)-methyl]-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester

HRID 71735

Reaction equation

HRID 71735 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH3:15][CH2:16][O:17][C:18]([CH:20]1[CH2:24][CH2:23][CH:22]([CH:25]=O)[N:21]1[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[O:19].[C:34]([O:38][C:39](=[O:42])[CH2:40][NH2:41])([CH3:37])([CH3:36])[CH3:35]>ClCCl>[CH3:15][CH2:16][O:17][C:18]([CH:20]1[CH2:24][CH2:23][CH:22]([CH2:25][NH:41][CH2:40][C:39]([O:38][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:42])[N:21]1[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[O:19]

Participants

5

Reactant 3

HCID 151417Glycine tert-butyl esterHCID 5049666Sodium triacetoxyborohydrideHCID 723380465-Formyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester

Product 1

HCID 666209305-[(Tert-butoxycarbonylmethyl-amino)-methyl]-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl esterYield 47.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Sodium triacetoxyborohydride (2.08 g, 9.86 mmol) was added to a solution of 5-formyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester (891 mg, 3.29 mmol) and glycine t-butyl ester (1.65 g, 9.86 mmol) in dichloromethane (20 mL) over 2 minutes—a small amount of gas evolution was observed. After 1 hour the reaction was quenched with saturated ammonium chloride (5 mL). The mixture was extracted with ethyl acetate (3×25 mL). The combined organic phases were dried over sodium sulfate, filtered and the solvent was removed under reduced pressure. The resulting residue was purified by flash chromatography with methanol and dichloromethane as the eluant at a gradient of 0-10%. The fractions containing product were combined and the solvent was removed under reduced pressure to provide 5-[(tert-butoxycarbonylmethyl-amino)-methyl]-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester (601 mg, 1.55 mmol, 47%). C19H34N2O6 calculated 386.2, observed [M+1]+ 387.2; rt=1.61 min.

Workup

  1. customAfter 1 hour the reaction was quenched with saturated ammonium chloride (5 mL)
  2. extractionThe mixture was extracted with ethyl acetate (3×25 mL)
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. filtrationfiltered
  5. customthe solvent was removed under reduced pressure
  6. customThe resulting residue was purified by flash chromatography with methanol and dichloromethane as the eluant at a gradient of 0-10%
  7. additionThe fractions containing product
  8. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-b0c9da1282674b34911a58bd57e5586c
Source dataset
uspto-grants-2014_09
Patent number
US08822430B2

Linked notes

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