Reaktion #58004

Reaktionsgleichung

hydrogen chloride

85

tert-butyl 4-(4,5-dimethyl-2-propionylphenyl)piperidine-1-carboxylate

DIEA

(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid

(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid hydrochloride salt

HATU

→

86

1-[2-(1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl]piperidin-4-yl)-4,5-dimethylphenyl]propan-1-one

Lösungsmittel

water

EtOAc

DCM

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeAfter 30 min the volatiles were evaporated in vacuo
2. 2
   Extraktionextracted three times with EtOAc
3. 3
   WaschenThe combined organic extracts were washed with brine
4. 4
   Trocknendried (MgSO4)
5. 5
   Filtrationfiltered
6. 6
   Einengenthe filtrate concentrated in vacuo
7. 7
   SonstigePurification of the crude residue by flash chromatography on silica gel (
8. 8
   Waschengradient elution
9. 9
   workup.ADDITION0%-20% methanol [containing 10% v/v ammonium hydroxide]/DCM as eluent)

Vorschrift

A saturated solution of hydrogen chloride in EtOAc (10 mL) was added to a solution of 85 (1.15 g, 3.33 mmol) in DCM (5.0 mL) at ambient temperature. After 30 min the volatiles were evaporated in vacuo. The above residue was resuspended in DCM (10 mL) and to this stirred solution was added DIEA (1.73 mL, 9.9 mmol), (3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid 80 (1.06 g, 3.3 mmol), and HATU (1.39 g, 3.6 mmol). After approximately 18 h, the reaction mixture was poured into water and extracted three times with EtOAc. The combined organic extracts were washed with brine, dried (MgSO4), filtered, and the filtrate concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 0%-20% methanol [containing 10% v/v ammonium hydroxide]/DCM as eluent) afforded 86 as a colorless oil.

Quelle