Реакция #58006

Уравнение реакции

hydrogen chloride

111

tert-butyl 4-[2-((1S)-1-{[(benzyloxy)carbonyl]amino}propyl)-4,5-dimethylphenyl]piperidine-1-carboxylate

DIEA

(3S,4R)-1-tert-butyl4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid

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

HATU

→

112

benzyl {(1S)-1-[2-(1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}piperidin-4-yl)-4,5-dimethylphenyl]propyl}carbamate

Растворители

water

EtOAc

DCM

Условия реакции

Обработка

1. 1
   ДругоеAfter 30 min the volatiles were evaporated in vacuo
2. 2
   Экстракцияextracted three times with DCM
3. 3
   ПромывкаThe combined organic extracts were washed with brine
4. 4
   Сушкаdried (MgSO4)
5. 5
   Фильтрацияfiltered
6. 6
   Концентрированиеthe filtrate concentrated in vacuo
7. 7
   ДругоеPurification of the crude residue by flash chromatography on silica gel (
8. 8
   Промывкаgradient elution
9. 9
   workup.ADDITION0%-10% methanol [containing 10% v/v ammonium hydroxide]/DCM as eluent)

Методика

A saturated solution of hydrogen chloride in EtOAc (10.0 mL) was added to a solution of 111 (830 mg, 1.7 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 (10.0 mL) and to this stirred solution was added DIEA (886 μL, 5.1 mmol), (3S,4R)-1-tert-butyl4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid 80 (542 mg, 1.7 mmol), and HATU (710 mg, 1.87 mmol). After approximately 18 h, the reaction mixture was poured into water and extracted three times with DCM. 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%-10% methanol [containing 10% v/v ammonium hydroxide]/DCM as eluent) afforded 112 as a colorless oil.

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