Imidazole → 2-bromo-(R)-1-tert-butyldimethylsiloxy-1-(3-formamido-4-benzyloxyphenyl)ethane

HRID 502005Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 502005
[Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].N1C=CN=C1.[Br:14][CH2:15][C@@H:16]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[C:20]([NH:32][CH:33]=[O:34])[CH:19]=1)[OH:17]>ClCCl>[Br:14][CH2:15][C@H:16]([O:17][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[C:20]([NH:32][CH:33]=[O:34])[CH:19]=1

Komponenten

5

Edukt 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 11142645(R)-N-[5-(2-Bromo-1-hydroxyethyl)-2-(phenylmethoxy)phenyl]formamide

Produkt 1

HCID 574610672-bromo-(R)-1-tert-butyldimethylsiloxy-1-(3-formamido-4-benzyloxyphenyl)ethaneAusbeute 91,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of tert-butyldimethylsilyl chloride (40.1 g, 0.26 mol) in dichloromethane (DCM) (37.5 mL) was added to a slurry of imidazole (21.86 g, 0.32 mol) and (R)-2-bromo-1-(3-formamido-4-benzyloxyphenyl)ethanol (74.54 g, 0.21 mol) in DCM (260 mL) over 8 min. The mixture was stirred for 22 h. The reaction was quenched with water (190 mL) and the aqueous layer was extracted with DCM (37.5 mL). The combined DCM layers were distilled at atmospheric pressure to a volume of ca. 110 mL. On cooling, spontaneous crystallisation occurred. Isooctane (750 mL) was added dropwise over 20 min. The slurry was cooled to 0° C. and the solids were collected by filtration then washed with 9:1 v/v isooctane:DCM (3×75 mL) and dried in vacuo to give the title compound as a colorless solid (89.65 g, 90% th). 1H NMR in accord with structure (400 MHz, CDCl3) δ(ppm): −0.06 (3H) s; 0.11(3H) s; *0.12 (3H) s; *0.89 (9H) s; 0.90 (9H) s; *3.38-3.49 (2H) m; 4.78-4.87 (1H) m; *5.09 (2H) s; 5.10 (2H) s; 6.96 (1H) d, J=8.6 Hz; *7.06 (1H) d of d, J=8.3, 2.0 Hz; 7.11 (1H) d of d, J=8.3 Hz, 2.0 Hz; 7.25-7.27 (1H) m; 7.36-7.45 (5H) m; *7.70 (1H) d, J=11.0 Hz; 7.79 (1H) s; 8.38 (1H) d, J=2.0 Hz; 8.42 (1H) d, J=1.5 Hz; *8.76 (1H) d, J=11.8 Hz. * Peaks are due to ca 25M% of the minor rotamer.

Aufarbeitung

  1. customThe reaction was quenched with water (190 mL)
  2. extractionthe aqueous layer was extracted with DCM (37.5 mL)
  3. distillationThe combined DCM layers were distilled at atmospheric pressure to a volume of ca. 110 mL
  4. temperatureOn cooling
  5. customspontaneous crystallisation
  6. additionIsooctane (750 mL) was added dropwise over 20 min
  7. filtrationthe solids were collected by filtration
  8. washthen washed with 9:1 v/v isooctane
  9. dry with materialDCM (3×75 mL) and dried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-905e6de8e2544f50a0d0a886d840a210
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07772434B2

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