1,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)- → Boc-Pro-D-Pro-OBn

HRID 1189911Notes

Reaction equation

HRID 1189911 reaction equation
CCN=C=NCCCN(C)C.Cl.[C:13]([N:20]1[CH2:27][CH2:26][CH2:25][C@H:21]1[C:22]([OH:24])=O)([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].[CH2:28]([O:35][C:36](=[O:42])[C@H:37]1[CH2:41][CH2:40][CH2:39][NH:38]1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>O1CCCC1>[N:20]1([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[CH2:27][CH2:26][CH2:25][C@H:21]1[C:22]([N:38]1[CH2:39][CH2:40][CH2:41][C@@H:37]1[C:36]([O:35][CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)=[O:42])=[O:24]

Participants

5

Reactant 3

HCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 736154benzyl (2R)-pyrrolidine-2-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 131731248Boc-Pro-D-Pro-OBnYield 75.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

5.75 g (30.0 mmol) of EDCl was added to 60 ml of tetrahydrofuran (THF) solution of 3.23 g (15.0 mmol) of N-Boc-L-Proline (manufactured by Tokyo Chemical Industry Co., Ltd) and 3.08 g (15.0 mmol) of D-Proline benzylester, followed by stirring for 18 hours at room temperature. After a reaction mixture was concentrated under reduced pressure, the concentrate was extracted by adding water and ethyl acetate. After an organic layer was washed sequentially with a diluted hydrochloric acid, an aqueous solution of sodium hydrogen carbonate and water (one time for each), it was concentrated under reduced pressure, thereby obtaining crude amide. The obtained amide compound was purified by a silica gel column chromatography (hexane/ethyl acetate=5/1 to 1/1 (volume ratio)), thereby obtaining 4.55 g of the product with a yield of 75.4%.

Workup

  1. concentrationAfter a reaction mixture was concentrated under reduced pressure
  2. extractionthe concentrate was extracted
  3. additionby adding water and ethyl acetate
  4. washAfter an organic layer was washed sequentially with a diluted hydrochloric acid
  5. concentrationan aqueous solution of sodium hydrogen carbonate and water (one time for each), it was concentrated under reduced pressure
  6. customobtaining crude amide
  7. customThe obtained amide compound was purified by a silica gel column chromatography (hexane/ethyl acetate=5/1 to 1/1 (volume ratio))

Sources & evidence

ORD record
ord-9d36ae207c894cf4b7afeb61bfb10dbb
Source dataset
uspto-grants-2014_03
Patent number
US08674144B2

Reaction notes

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