反応 #74197

反応方程式

acid chloride toluene

6-Phenyl-pyridine-2-carbonyl chloride

sodium carbonate

water

L-threonine

→

title compound

収率 94.0%

(2S,3R)-3-Hydroxy-2-[oxo-2-(6-phenyl-pyridin-2-yl)-ethyl}-butyric acid

収率 94.0%

溶媒

toluene

反応条件

後処理

1. 1
   workup.ADDITIONOnce the addition
2. 2
   温度the reaction was warmed to room temperature (˜22-25° C.)
3. 3
   その他typically ˜3 hr
4. 4
   その他The reaction mixture was then transferred to a separatory funnel
5. 5
   その他the two layers were separated
6. 6
   workup.ADDITIONMethanol (800 mL) was then added to the mixture
7. 7
   その他at 15-20° C
8. 8
   その他followed by precipitation of the product at pH=3
9. 9
   workup.STIRRINGto stir at room temperature for 30 minutes post pH adjustment
10. 10
    ろ過The white solid was collected by vacuum filtration, (mother liquor losses <2 mg/mL),
11. 11
    洗浄washed with deionized water (2×500 ml)
12. 12
    その他then dried in a vacuum oven at 40° C. with a nitrogen sweep to a constant weight

実験手順

A 3-L three neck round bottomed flask was equipped with an overhead stirrer, thermocouple, pressure equalizing dropping funnel, nitrogen inlet/outlet and ice/water cooling bath. L-threonine, 62.8 g (0.53 mol) was added, followed by 117 g (1.1 mol) of sodium carbonate and 1500 mL of deionized water. The aqueous solution was cooled to 10.0° C. During this time the addition funnel was charged with the acid chloride/toluene solution prepared in Step A. This toluene solution was added dropwise to the aqueous reaction over approximately 10 minutes at ˜10° C. Once the addition was complete, the reaction was warmed to room temperature (˜22-25° C.) and vigorously stirred until it was shown to be complete by HPLC analysis (typically ˜3 hr). The reaction mixture was then transferred to a separatory funnel and the two layers were separated. The lower aqueous phase was then recharged to the reaction flask. Methanol (800 mL) was then added to the mixture followed by pH adjustment (target pH=1-2) with 2.5M HCl (˜850 mL), keeping the temperature at 15-20° C. Some off-gassing occurred at ˜pH=5, followed by precipitation of the product at pH=3. The slurry was allowed to stir at room temperature for 30 minutes post pH adjustment. The white solid was collected by vacuum filtration, (mother liquor losses <2 mg/mL), washed with deionized water (2×500 ml) then dried in a vacuum oven at 40° C. with a nitrogen sweep to a constant weight to provide 141 g (0.471 mol, 94%) of the title compound with an HPLC purity of 99 A % (95 wt %). 1H NMR (d6-DMSO, 400 MHz) δ 12.9 (s, 1H, b), 8.71 (d, 1H, J=9.16 Hz), 8.23 (d, 1H, J=7.24 Hz), 8.1 (m, 3H), 8.03 (d, 1H, J=7.0 Hz), 7.55 (m, 3H), 5.34 (s, 1H, b), 4.46 (dd, 1H, J=2.52, 9.16 Hz), 4.34 (dd, 1H, J=1.92, 6.24 Hz), 1.15 (d, 3H, J=6.4 Hz).

出典