Reaktion #340067

Reaktionsgleichung

3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic acid

HATU

5-amino-1-pentanol

DIPEA

DIPEA

→

title intermediate

Ausbeute 80.1%

Biphenyl-2-ylcarbamic Acid 1-[2-(5-Oxopentylcarbamoyl)ethyl]piperidin-4-yl Ester

Ausbeute 80.1%

Lösungsmittel

DCM

DMSO

Reaktionsbedingungen

Aufarbeitung

1. 1
   WaschenThe reaction mixture was then washed with brine (100 mL), water (100 mL)
2. 2
   Trocknendried over magnesium sulfate
3. 3
   Filtrationfiltered
4. 4
   Einengenconcentrated
5. 5
   workup.DISSOLUTIONThe residue was dissolved in DCM (100 mL)
6. 6
   Temperaturcooled down to −5° C. in an ice/brine bath
7. 7
   workup.STIRRINGThe reaction mixture was stirred at 0° C. for 2 hours
8. 8
   Waschenwashed with water (100 mL) and brine (2×100 mL)
9. 9
   TrocknenThe organic layer was dried over magnesium sulfate
10. 10
    Filtrationfiltered
11. 11
    Einengenconcentrated

Vorschrift

A mixture of 3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic acid (5 g, 13.5 mmol; prepared as described in Preparation 10), HATU (10.3 g, 27 mmol), 5-amino-1-pentanol (1.67 g, 16.2 mmol) and DIPEA (7.04 mL, 40.5 mmol) in 100 mL of DCM was stirred at room temperature for 1 hour. The reaction mixture was then washed with brine (100 mL), water (100 mL), dried over magnesium sulfate, filtered and concentrated. The residue was dissolved in DCM (100 mL) and cooled down to −5° C. in an ice/brine bath. DIPEA (7.04 mL, 40.5 mmol) and DMSO (10 mL) were added to the solution, followed by sulfur trioxide pyridine complex (6.45 g, 40.5 mmol). The reaction mixture was stirred at 0° C. for 2 hours and then washed with water (100 mL) and brine (2×100 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated to yield 4.88 g of the title intermediate (80% yield) as a semi-solid.

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