Reaktion #160664

Reaktionsgleichung

6

2-(Bromomethyl)-6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylpyridine

LHMDS

diisopropyl (R)-(+)-malate

→

4b

Ausbeute 70.0%

(2S,3R)-Diisopropyl 2-((6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylpyridin-2-yl)methyl)-3-hydroxysuccinate

Ausbeute 70.0%

Lösungsmittel

THF

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethen transferred to an ice-bath
2. 2
   workup.WAIT(0° C.) for 30 min
3. 3
   TemperaturThe reaction was maintained at −78° C. for an additional 30 min
4. 4
   Sonstigethen transferred to an ice-bath
5. 5
   Temperaturslowly warm to room temperature
6. 6
   workup.WAITAfter 2 h
7. 7
   Sonstigethe reaction was quenched with NH4Cl (1 mL)
8. 8
   Sonstigethen partitioned between EtOAc (200 mL) and saturated NH4Cl (150 mL)
9. 9
   ExtraktionThe inorganic layer was extracted with EtOAc (150 mL)
10. 10
    WaschenThe combined organic layer was washed by H2O (100 mL), brine (100 mL)
11. 11
    Trocknendried over Na2SO4
12. 12
    Einengenconcentrated
13. 13
    SonstigeThe crude yellow oil was purified by flash column chromatography (EtOAc/hexanes, 1:9-1:4)

Vorschrift

To a dry flask containing THF (20 mL) at −78° C. was added fresh LHMDS (1.0 M in THF, 10 mL, 10 mmol). After 10 min, a solution of diisopropyl (R)-(+)-malate (5b, 1008 μL, 4.88 mmol) was added dropwise as a solution in THF (5 mL) through a cannula. The reaction was stirred at the same temperature for 10 min then transferred to an ice-bath (0° C.) for 30 min. The reaction was cooled to −78° C. again and 6 (1017 mg, 3.66 mmol) was added slowly (1 drop/sec) as a solution in THF (5 mL) through a cannula. The color of the reaction mixture turned light purple. The reaction was maintained at −78° C. for an additional 30 min then transferred to an ice-bath and slowly warm to room temperature. After 2 h, the reaction was quenched with NH4Cl (1 mL) then partitioned between EtOAc (200 mL) and saturated NH4Cl (150 mL). The inorganic layer was extracted with EtOAc (150 mL). The combined organic layer was washed by H2O (100 mL), brine (100 mL), dried over Na2SO4, and concentrated. The crude yellow oil was purified by flash column chromatography (EtOAc/hexanes, 1:9-1:4) to give 4b (1.76 g, 2.56 mmol, 70%) as a pale yellow oil (without detection of any cis-isomer): 1H NMR (500 MHz, CDCl3) δ 1.14-1.15 (d, J=6.5 Hz, 3H), 1.17-1.18 (d, J=6.0 Hz, 3H), 1.25-1.26 (d, J=6.5 Hz, 3H), 1.29-1.30 (d, J=6.0 Hz, 3H), 2.13 (s, 6H), 2.41 (s, 3H), 3.10-3.15 (dd, J=8.5, 14.0 Hz, 1H), 3.34-3.40 (m, 2H), 3.72-3.76 (dt, J=2.5, 8.0 Hz, 1H), 4.07-4.09 (dd, J=2.5, 7.0 Hz, 1H), 4.96-5.01 (m, 1H), 5.09-5.15 (m, 1H), 5.90 (s, 2H), 6.89 (s, 1H), 7.10 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 13.5, 21.2, 21.8, 21.9, 22.0, 36.1, 48.0, 68.8, 70.1, 70.6, 107.0, 120.7, 124.1, 128.7, 150.1, 158.7, 171.5, 173.4; LCQ-MS (M+H+) calcd for C23H33N2O5 417. found 417; LC-TOF-MS (M+H+) calcd for C23H33N2O5 417.23895. found 417.23834.

Quelle