Ethyl Acetate → (3R,4S)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-((S)-1-phenyl-propylcarbamoyloxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1158431

Reaktionsgleichung

Reaktionsgleichung von HRID 1158431
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:33])[CH3:32])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[C@H:10]([CH2:34][OH:35])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1([C@@H:42]([N:45]=[C:46]=[O:47])[CH2:43][CH3:44])C=CC=CC=1.[Al+3].[Cl-].[Cl-].[Cl-].CCO[C:55]([CH3:57])=O>CCOCC>[C:1]([O:5][C:6]([N:8]1[CH2:9][C@@H:10]([C@H:34]([O:35][C:46](=[O:47])[NH:45][CH2:42][CH2:43][CH3:44])[C:57]2[CH:55]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C@H:11]([CH2:13][N:14]([CH:31]([CH3:32])[CH3:33])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[CH2:12]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Komponenten

6

Edukt 4

HCID 8857Ethyl AcetateHCID 6451240Aluminum(III) Chloride2×HCID 7018275[(1S)-1-isocyanatopropyl]benzene2×HCID 59512299(3S,4R)-3-Hydroxymethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 68617439(3R,4S)-3-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-((S)-1-phenyl-propylcarbamoyloxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3283Diethyl EtherLösungsmittel

Versuchsvorschrift

To a solution of (3S,4R)-3-hydroxymethyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (200 mg, 0.404 mmol) in ether (12 mL) are successively added (S)-1-phenylpropyl isocyanate (130.4 mg, 0.809 mmol) and AlCl3 (54 mg, 0.404 mmol). The mixture is stirred at RT under nitrogen overnight. (S)-1-phenylpropyl isocyanate (150 μL) and AlCl3 (54 mg, 0.404 mmol) are again added and the mixture further stirred for 5 h. AcOEt is added and the reaction mixture quenched by the addition of an aqueous saturated solution of NaHCO3. The layers are separated and the aqueous one back extracted twice with AcOEt. The combined organic extracts are dried over Na2SO4, filtered and concentrated under reduced pressure. The crude mixture is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 100:0 to 95:5) to give the title product TLC, Rf (CH2Cl2/MeOH 95:5)=0.35. MS (LC-MS): 656.2 [M+H]+; tR (HPLC, Nucleosil C18-HD column, 20-100% CH3CN/H2O/6 min, 100% CH3CN/1.5 min, flow: 1 ml/min): 3.94 min.

Aufarbeitung

  1. stirringthe mixture further stirred for 5 h
  2. customthe reaction mixture quenched by the addition of an aqueous saturated solution of NaHCO3
  3. customThe layers are separated
  4. extractionthe aqueous one back extracted twice with AcOEt
  5. dry with materialThe combined organic extracts are dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude mixture is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 100:0 to 95:5)

Quellen und Nachweise

ORD-Eintrag
ord-72a18a1da1d94972b772a9206006d253
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07807709B2

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