1,2-Dichloroethane → (R)-Benzyl 2-(pyrrolidine-1-carbonyl)pyrrolidine-1-carboxylate

HRID 425926

Reaction equation

HRID 425926 reaction equation
[C:1]([N:11]1[CH2:18][CH2:17][CH2:16][C@@H:12]1[C:13]([OH:15])=O)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C(Cl)CCl.[CH:23]1[CH:24]=CC2N(O)N=[N:29][C:27]=2[CH:28]=1.N1CCCC1>CN(C=O)C.O.C(=O)(O)[O-].[Na+]>[CH2:4]([O:3][C:1]([N:11]1[CH2:18][CH2:17][CH2:16][C@@H:12]1[C:13]([N:29]1[CH2:24][CH2:23][CH2:28][CH2:27]1)=[O:15])=[O:2])[C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 31268PyrrolidineHCID 757711-HydroxybenzotriazoleHCID 1112081-benzyl hydrogen (R)-pyrrolidine-1,2-dicarboxylate

Product 1

HCID 667614(R)-Benzyl 2-(pyrrolidine-1-carbonyl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of (+)-carbobenzyloxy-D-proline (1.5 g, 6 mmol), EDC (2.3 g, 12 mmol), HOBt (800 mg, 6 mmol), TEA (1.5 mL) and pyrrolidine (853 mg, 12 mmol) in DMF (20 mL) was stirred at rt for 18 hr. The reaction was diluted with water and sodium bicarbonate, extracted with dichloromethane (3×). The combined DCM was concentrated and purified on a silica gel column to give (R)-2-(pyrrolidine-1-carbonyl)-pyrrolidine-1-carboxylic acid benzyl ester. (R)-2-(pyrrolidine-1-carbonyl)-pyrrolidine-1-carboxylic acid benzyl ester was hydrogenated using Pd/C in methanol at ambient temperature for 20 hr to provide pyrrolidin-1-yl-(R)-pyrrolidin-2-yl-methanone. To a solution of pyrrolidin-1-yl-(R)-pyrrolidin-2-yl-methanone (1.2 g, 7.1 mmol) in THF (10 mL) at 0° C. was added B2H6 (10 mL, 10 mmol). The mixture was heated to reflux for 16 hr. The reaction was acidified with HCl and concentrated. The residue was basified to pH 10 with 2N NaOH and extracted with 5% methanol in DCM. The organic layer was concentrated and purified on a silica gel column to give 800 mg (73%) of (R)-2-pyrrolidin-1-ylmethyl-pyrrolidine.

Workup

  1. extractionextracted with dichloromethane (3×)
  2. concentrationThe combined DCM was concentrated
  3. custompurified on a silica gel column

Sources & evidence

ORD record
ord-301dfed0c24b42129892308a3c4c5512
Source dataset
uspto-grants-2012_01
Patent number
US08106197B2

Linked notes

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