Trifluoroacetic acid → HCID 25160352, Verbindung

A stirred solution of (R)-3-(tert-butyldimethylsilyloxy)-N-(tert-butoxycarbonyl)pyrrolidine (1.00 g, 3.32 mmol) and dirhodium(II) tetrakis[(S)—N-[p-(dodecylphenyl)sulfonyl]prolinate] {Rh2(R-DOSP)4} (125 mg, 0.07 mmol) in 2,2-dimethylbutane was stirred under reflux. Diazo-(3,4-dichlorophenyl)acetic acid methyl ester (1.63 g, 6.64 mmol) in a 1:4 mixture of trifluorotolune: 2,2-diethylbutane was added via syringe pump over a 3 hour period. The mixture was stirred under reflux for an additional 2 hours and then stirred at room temperature overnight. The mixture was then concentrated, diluted with dichloromethane (100 mL) and charged with trifluoroacetic acid (1.97 mL, 26.6 mmol). After 16 hours, the solution was concentrated, the residue dissolved in Et2O (100 mL), and extracted with 10% HCl (3×100 mL). The aqueous layers were basified with solid NaHCO3 (solid) and 1M NaOH to pH=8−9. The aqueous phase was then back extracted ethyl acetate (3×50 mL) and the organic phases were washed with brine (25 mL), dried with Na2SO4, and filtered. The extraction was reduced and purified by chromatography to afford the titled compound as a clear oil: 391 mg (35% yield). 1H NMR (500 MHz, CDCl3) δ 7.50 (s, 1H), 7.41-7.39 (d, J=8 Hz, 1H), 7.24-7.22 (m, 1H), 4.41 (m, 1H), 3.99 (m, 1H), 3.67 (s, 1H), 3.42 (d, J=9 Hz, 1H), 3.04 (dd, J=4.5, 7.5 Hz, 1H), 2.83 (m, 1H), 2.00 (m, 4H), 1.66 (m, 1H). 13C NMR (75 MHz, CDCl3) δ 172.3 (C), 137.4 (C), 132.7 (C), 131.8 (C), 130.6 (CH), 130.5 (CH), 128.1 (CH), 72.3 (CH), 59.3 (CH2), 56.6 (CH), 54.8 (CH), 52.2 (CH3), 40.2 (CH2); IR (neat): 1753 cm−1; HRMS (ESI) m/z Calc'd for [C13H15Cl2NO3]+ (M+): 303.0429. Found: 303.0437.

1. temperatureunder reflux
2. additionwas added via syringe pump over a 3 hour period
3. temperatureunder reflux for an additional 2 hours
4. stirringstirred at room temperature overnight
5. concentrationThe mixture was then concentrated
6. additiondiluted with dichloromethane (100 mL)
7. concentrationthe solution was concentrated
8. dissolutionthe residue dissolved in Et2O (100 mL)
9. extractionextracted with 10% HCl (3×100 mL)
10. washback extracted ethyl acetate (3×50 mL) and the organic phases were washed with brine (25 mL)
11. dry with materialdried with Na2SO4
12. filtrationfiltered
13. extractionThe extraction
14. custompurified by chromatography

ORD-Eintrag

ord-cfe57ade015c40da9b2b71e8e5299b4f

Quelldatensatz

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08329741B2