Sodium Hydroxide → (s)-3-[1-(2,4-Dichlorophenyl)-ethylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 252098

Reaktionsgleichung

Reaktionsgleichung von HRID 252098
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([NH2:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:14][C:15]([C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=1[Cl:24])=O.[BH4-].[Na+].[OH-].[Na+]>C1(C)C=CC=CC=1>[CH3:15][CH:17]([CH2:18][CH2:19][CH3:20])[CH3:22].[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([NH:13][CH:15]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=2[Cl:24])[CH3:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Komponenten

7

Edukt 4

HCID 14798Sodium HydroxideHCID 166932',4'-DichloroacetophenoneHCID 854071tert-butyl (3S)-3-aminopyrrolidine-1-carboxylateHCID 4311764Sodium borohydride

Produkt 2

HCID 78922-MethylpentaneHCID 66853965(s)-3-[1-(2,4-Dichlorophenyl)-ethylamino]-pyrrolidine-1-carboxylic acid tert-butyl esterAusbeute 56,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 1140TolueneLösungsmittel

Versuchsvorschrift

Stir a mixture of (S)-3-aminopyrrolidine-1-carboxylic acid tert-butyl ester (10.4 g, 55.7 mmol) and 2,4-dichloroacetophenone (10.5 g, 55 mmol) in dry toluene (400 mL) at 110° C. for 48 h. Concentrate and dissolve the residue in methanol (160 mL), add sodium borohydride (3.37 g, 89 mmol) slowly and stir for 20 min. Add 1 N sodium hydroxide (200 mL) and extract with diethyl ether. Combine the organic layers, wash with water, dry (magnesium sulfate), concentrate and chromatograph on silica gel, eluting with 0:100 to 40:60 ethyl acetate:2-methylpentane to give (S)-3-[1-(2,4-dichlorophenyl)-ethylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (5.6 g, 28%). 1H NMR (300 MHz, CDCl3) δ 7.41-7.51 (1H, m), 7.34 (1H, s), 7.24 (1H, dd, J=8.38, 1.98 Hz), 4.21-4.36 (1H, m), 3.42-3.57 (2H, m), 3.21-3.33 (1H, m), 3.04-3.15 (1H, m), 2.88-3.03 (1H, m), 1.96-2.05 (1H, m), 1.63-1.72 (1H, m), 1.37-1.47 (9H, m), 1.30 (3H, dd, J=6.59, 1.51 Hz), MS (ES): m/z=359[M+].

Aufarbeitung

  1. concentrationConcentrate
  2. dissolutiondissolve the residue in methanol (160 mL)
  3. stirringstir for 20 min
  4. extractionextract with diethyl ether
  5. washwash with water
  6. dry with materialdry (magnesium sulfate)
  7. concentrationconcentrate
  8. washchromatograph on silica gel, eluting with 0:100 to 40:60 ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-34b057b6c0c749299f89cfbf2235a42e
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07868014B2

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