تفاعل #310058

معادلة التفاعل

2-aminopyridine-3-carboxaldehyde

THF

KMnO4

→

product

1-(2-amino-3-pyridinyl)ethanol

ظروف التفاعل

المعالجة

1. 1
   أخرىTo a dry flask (dried with a heat gun under argon
2. 2
   أخرىpurge)
3. 3
   workup.ADDITIONwas added dry THF (400 mL) and MeLi—LiBr (137 mL of a 1.5 M solution in Et2O, 204.9 mmol) via cannula
4. 4
   workup.ADDITIONwas added dropwise via a pressure
5. 5
   workup.ADDITIONaddition funnel over ˜45 min
6. 6
   workup.ADDITIONUpon complete addition
7. 7
   أخرىThe reaction was quenched very carefully with water (200 mL
8. 8
   workup.ADDITIONdropwise initially), diluted with EtOAc (200 mL)
9. 9
   أخرىThe layers were separated
10. 10
    استخلاصthe aqueous layer was extracted with 3% MeOH in EtOAc
11. 11
    تجفيفThe combined extracts were dried over sodium sulfate
12. 12
    ترشيحfiltered
13. 13
    تركيزconcentrated under reduced pressure
14. 14
    أخرىThe residue was purified by silica gel chromatography (Analogix; 0 to 5% MeOH in EtOAc)

الإجراء التجريبي

To a dry flask (dried with a heat gun under argon purge) was added dry THF (400 mL) and MeLi—LiBr (137 mL of a 1.5 M solution in Et2O, 204.9 mmol) via cannula. This solution was cooled to −78° C. when a solution of 2-aminopyridine-3-carboxaldehyde (10.0 g, 82.0 mmol) in THF (150 mL) was added dropwise via a pressure equalizing addition funnel over ˜45 min with vigorous stirring (exotherm observed, orange color persisted). Upon complete addition, the solution was allowed to stir for 1 hour at −78° C., at which time TLC (KMnO4 stain with heat) indicated that most of the starting material had been converted to product. The reaction was quenched very carefully with water (200 mL; dropwise initially), diluted with EtOAc (200 mL) and allowed to warm to rt. The layers were separated and the aqueous layer was extracted with 3% MeOH in EtOAc. The combined extracts were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (Analogix; 0 to 5% MeOH in EtOAc) to give 7.78 g (68%) of the desired racemic product as a yellow oil that solidified under high vac over several days. This material was separated into its respective enantiomers (>98% ee) by SFC with a chiralcel OD-H (20×250 mm) column (10% EtOH/0.1% isopropylamine in heptane/0.1% isopropylamine).

المصدر