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

HRID 1766747

Reaktionsgleichung

Reaktionsgleichung von HRID 1766747
[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

Komponenten

8

Edukt 4

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 516892Sodium BicarbonateLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-f767b2427bb0460981113ea4e4642add
Quelldatensatz
uspto-grants-2007_06
Patentnummer
US07230098B2

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