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1,2-Dichloroethane → di-tert-butyl [(3R)-6-(2,3-dichlorophenyl)-2-oxoazepan-3-yl]imidodicarbonate

HRID 493632
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 493632
[C:1]([O:5][C:6]([N:8]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C@@H:9]([C:23](OCC1C=CC=CC=1)=[O:24])[CH2:10][CH2:11][CH:12]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[C:16]=1[Cl:22])[CH2:13][NH2:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>CO.O.C(Cl)Cl>[Cl:22][C:16]1[C:17]([Cl:21])=[CH:18][CH:19]=[CH:20][C:15]=1[CH:12]1[CH2:13][NH:14][C:23](=[O:24])[C@H:9]([N:8]([C:33]([O:35][C:36]([CH3:39])([CH3:37])[CH3:38])=[O:34])[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:10][CH2:11]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

11

Edukt 7

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 181649HOAtHCID 516892Sodium BicarbonateHCID 86595032Benzyl N2,N2-bis(tert-butoxycarbonyl)-5-(2,3-dichlorophenyl)-D-lysinate

Produkt 1

HCID 66939423di-tert-butyl [(3R)-6-(2,3-dichlorophenyl)-2-oxoazepan-3-yl]imidodicarbonateAusbeute 82,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

To a solution benzyl N2,N2-bis(tert-butoxycarbonyl)-5-(2,3-dichlorophenyl)-D-lysinate (0.45 g, 0.77 mmol) in MeOH (4 mL) and water (2 mL) was added 1N NaOH (3.1 mL, 3.1 mmol). This solution was heated to 40° C. for 6 h, then neutralized with 1N HCl and concentrated. To a solution of this residue in DCM (10 mL) were added EDC (0.19 g, 0.97 mmol) and HOAT (53 mg, 0.39 mmol) followed by triethylamine (0.32 mL, 0.73 mmol). After 2 h, NaHCO3 was added, the layers separated and the aqueous phase backwashed with DCM. The combined organics were dried over magnesium sulfate, filtered and concentrated. This residue was purified by silica gel chromatography (0.5%→10% MeOH/DCM) to give di-tert-butyl [(3R)-6-(2,3-dichlorophenyl)-2-oxoazepan-3-yl]imidodicarbonate (300 mg). MS 473 (M+1). Standard deprotection of a portion of this material gave the title product. MS 273 (M+1).

Aufarbeitung

  1. concentrationconcentrated
  2. customthe layers separated
  3. dry with materialThe combined organics were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThis residue was purified by silica gel chromatography (0.5%→10% MeOH/DCM)

Quellen und Nachweise

ORD-Eintrag
ord-27afc7ea79b34529b2157a967e207fe9
Quelldatensatz
uspto-grants-2009_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07534784B2

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