1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1,1-Dimethylethyl (2R)-2-[(4-hydroxy-1-piperidinyl)carbonyl]-1-pyrrolidinecarboxylate

HRID 1359857Notes

Reaction equation

HRID 1359857 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[NH:37]1[CH2:42][CH2:41][CH:40]([OH:43])[CH2:39][CH2:38]1>CN(C=O)C.O.C(=O)(O)[O-].[Na+]>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[C:13]([N:37]1[CH2:42][CH2:41][CH:40]([OH:43])[CH2:39][CH2:38]1)=[O:15])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 79341Piperidin-4-olHCID 688022(2R)-1-[(tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acid

Product 1

HCID 699936691,1-Dimethylethyl (2R)-2-[(4-hydroxy-1-piperidinyl)carbonyl]-1-pyrrolidinecarboxylateYield 93.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of (R)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (2 g, 9.3 mmol), EDAC (3.5 g, 16 mmol), HOBt (1.4 g, 18 mmol), TEA (2.5 mL) and piperidin-4-ol (1.8 g, 16 mmol) in DMF (20 mL) was stirred at rt for 20 hours. The reaction was diluted with water and sodium bicarbonate, extracted with 5% methanol in DCM. The DCM was concentrated and purified on a silica gel column to give 2.6 g of (R)-2-(4-hydroxy-piperidine-1-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester.

Workup

  1. extractionextracted with 5% methanol in DCM
  2. concentrationThe DCM was concentrated
  3. custompurified on a silica gel column

Sources & evidence

ORD record
ord-e033e4dd2e704060b0375e05ae647f46
Source dataset
uspto-grants-2003_07
Patent number
US06599902B2

Reaction notes

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