Reaktion #807018

Reaktionsgleichung

1-Chloroisoquinoline

MeOH CH2Cl2

Boc-L-4-hydroxyproline

t-BuOK

→

4-(isoquinolin-1-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester

Ausbeute 96.0%

Lösungsmittel

DMSO

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwas cooled in an ice bath for ˜3 minutes
2. 2
   workup.WAITwas continued for a few minutes until a solid mass
3. 3
   Sonstigeformed
4. 4
   Sonstigeto give a clear colorless solution
5. 5
   workup.STIRRINGThe reaction was stirred for 24 h at rt
6. 6
   SonstigeThe dark reaction mixture
7. 7
   Sonstigewas partitioned between ether (200 mL) and water (600 mL)
8. 8
   ExtraktionThe resulting milky yellow solution was extracted with ether (4×200 mL)
9. 9
   TrocknenThe combined ether extracts were dried (MgSO4)
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated in vacuo
12. 12
    Sonstigeto give a golden oil

Vorschrift

A suspension of Boc-L-4-hydroxyproline (N-Boc(2S,4R)-hydroxyproline) (3.85 g 16.6 millimole (“mmol”) (CHEM-IMPEX International) in DMSO (60 mL) was cooled in an ice bath for ˜3 minutes, and then t-BuOK (4.66 g, 41.5 mmol) was added. Stirring and cooling in the ice bath was continued for a few minutes until a solid mass formed. At this time the reaction mixture was allowed to warm to rt over 1.5 h to give a clear colorless solution. 1-Chloroisoquinoline (3.0 g, 18.3 mmol) was added in two portions 10 min apart. The reaction was stirred for 24 h at rt. The dark reaction mixture was partitioned between ether (200 mL) and water (600 mL). The aqueous phase was acidified to pH 4 using 4N HCl. The resulting milky yellow solution was extracted with ether (4×200 mL). The combined ether extracts were dried (MgSO4), filtered, and concentrated in vacuo to give a golden oil. Flash chromatography (2–4% MeOH/CH2Cl2) gave 5.69 g (96%) of 4-(isoquinolin-1-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester as an off-white solid: LC-MS (Method A, retention time: 3.06 min), MS m/z 359 (M++1).

Quelle