tert-butyl N-(2-hydroxyethyl)carbamate → {4-[4-(2-tert-Butoxycarbonylaminoethoxy)phenyl]butyl}carbamic acid benzyl ester

HRID 81320

Reaktionsgleichung

Reaktionsgleichung von HRID 81320
CC(OC(/N=N/C(OC(C)C)=O)=O)C.[CH2:15]([O:22][C:23](=[O:36])[NH:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([OH:35])=[CH:31][CH:30]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[C:37]([O:41][C:42](=[O:47])[NH:43][CH2:44][CH2:45]O)([CH3:40])([CH3:39])[CH3:38]>C1COCC1>[CH2:15]([O:22][C:23](=[O:36])[NH:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([O:35][CH2:45][CH2:44][NH:43][C:42]([O:41][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:47])=[CH:31][CH:30]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Komponenten

5

Edukt 3

HCID 2733206tert-butyl N-(2-hydroxyethyl)carbamateHCID 5363146Diisopropyl azodicarboxylateHCID 11637991N-Cbz4-(4-hydroxyphenyl)butylamine

Produkt 1

HCID 67364654{4-[4-(2-tert-Butoxycarbonylaminoethoxy)phenyl]butyl}carbamic acid benzyl esterAusbeute 73,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

Diisopropylazodicarboxylate (132 mL) was added dropwise over 45 minutes to a stirring mixture of [4-(4-hydroxyphenyl)butyl]carbamic acid benzyl ester (50 g, 0.167 mol), (2-hydroxyethyl)carbamic acid tert-butyl ester (103.4 mL, 0.668 mol), and THF (150 mL) with ice-methanol bath cooling from 15 to 35° C. When the exothermic reaction ceased, the cooling bath was removed, and the reaction was allowed to stir at room temperature overnight. The solvent was evaporated at reduced pressure, and the residue was applied to a 1 kg column of silica gel and eluted with methylene chloride. The chromatography was repeated twice. The residue after evaporation was washed with hexanes (1.5 L), and the resulting solid was re-crystallized from a mixture of hexanes and methylene chloride (4:1, 1 L) to afford 54 g (73%) of the pure product as a white solid. A second crop yielded an additional 10 g (13%) of the product. 1H NMR (300 MHz, CDCl3) δ 1.45 (s, 9H), 1.56 (m, 4H), 2.56 (t, 2H), 3.20 (m, 2H), 3.50 (m, 2H), 3.98 (t, 2H), 4.75 (br s, 1H), 5.00 (br s, 1H), 5.09 (s, 2H), 6.80 (d, 2H), 7.06 (d, 2H), 7.34 (m, 5H).

Aufarbeitung

  1. customWhen the exothermic reaction
  2. customthe cooling bath was removed
  3. customThe solvent was evaporated at reduced pressure
  4. washeluted with methylene chloride
  5. customThe residue after evaporation
  6. washwas washed with hexanes (1.5 L)
  7. customthe resulting solid was re-crystallized from a mixture of hexanes and methylene chloride (4:1, 1 L)

Quellen und Nachweise

ORD-Eintrag
ord-1b7a4abb290c4e25b96720121e1343f8
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846688B2

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