Reaktion #8727

Reaktionsgleichung

DIAD

4-chloro-3-hydroxyphenylcarbamic acid tert-butyl ester

(S)-1-methyl-pyrrolidin-3-ol

triphenylphosphine

→

title compound

Ausbeute 80.0%

4-Chloro-3-((R)-1-methyl-pyrrolidin-3-yloxy) aniline

Ausbeute 80.0%

Lösungsmittel

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturmaintained for 16 h
2. 2
   SonstigeThe THF was removed in vacuo
3. 3
   workup.ADDITIONthe residue treated with 6 N HCl (650 mL)
4. 4
   workup.ADDITIONwas diluted with water (500 mL)
5. 5
   Filtrationthe filtered
6. 6
   Sonstigeto remove the triphenylphosphine oxide
7. 7
   WaschenThe filtrate was washed with EtOAc (3×1 L) and chloroform (5×1 L)
8. 8
   Sonstigeto remove additional reaction by-products
9. 9
   Extraktionextracted with ether (2×1 L) and EtOAc (2×1 L)
10. 10
    WaschenThe combined organic layers were washed with saturated NaHCO3 (2×1 L) and brine (1 L)
11. 11
    Trocknendried (MgSO4)
12. 12
    Einengenconcentrated

Vorschrift

To a cooled (0° C.) solution of 4-chloro-3-hydroxyphenylcarbamic acid tert-butyl ester (55 g, 0.23 mol), (S)-1-methyl-pyrrolidin-3-ol (24 g, 0.24 mol), and triphenylphosphine (89 g, 0.34 mol) in THF (1.1 L) was added dropwise via addition funnel a solution of DIAD (67 mL, 0.34 mol) in THF (100 mL) over 1 h. The resultant solution was allowed to slowly warm to ambient temperature and maintained for 16 h. The THF was removed in vacuo and the residue treated with 6 N HCl (650 mL). The resultant mixture was stirred at room temperature for 4 h, at which time it was diluted with water (500 mL) and the filtered to remove the triphenylphosphine oxide. The filtrate was washed with EtOAc (3×1 L) and chloroform (5×1 L) to remove additional reaction by-products. The aqueous layer was then basified with solid NaOH pellets and extracted with ether (2×1 L) and EtOAc (2×1 L). The combined organic layers were washed with saturated NaHCO3 (2×1 L) and brine (1 L), dried (MgSO4), and concentrated to give 40 g (80%) of the title compound: MS (ES+) m/e [M+H]+ 227.

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