Reaction #1869167

Reaction equation

propionaldehyde

2-(2,5-dimethylpyrrol-1-yl)-5-oxiranylpyridine

(S)-(+)-2-amino-1-propanol

acetic acid

Sodium triacetoxyborohydride

→

(2S)-2-[{(RS)-2-[6-(2,5-dimethyl-1H-pyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl}propylamino]propan-1-ol

Yield 89.0%

Solvents

water

DCM

toluene

Conditions

Workup

1. 1
   Temperaturewas heated
2. 2
   Temperatureto reflux overnight
3. 3
   Otherto separate
4. 4
   Temperaturedropwise maintaining the temperature below 30° C
5. 5
   Otherbefore quenching with water (1.20 L)
6. 6
   Otherto separate
7. 7
   ExtractionThe aqueous phase was extracted with DCM (1.20 L)
8. 8
   Washthe combined organic phases washed with water (0.60 L), water (0.30 L)
9. 9
   Concentrationconcentrated in vacuo
10. 10
    OtherYield 89% (0.89 Kg, the material was isolated in approximately 70% purity) δH (CDCl3, 300 MHz) 0.8-1.0 (6H, m), 1.50-1.70 (2H, m), 2.10 (6H, s), 2.50-3.15 (5H, m), 3.50 (2H, dd), 4.80 (1H, dd), 5.90 (2H, s), 7.20 (1H, m), 7.80-7.90 (1H, m), 8.60 (1H, m) ppm

Procedure

A mixture of 2-(2,5-dimethylpyrrol-1-yl)-5-oxiranylpyridine (0.65 Kg, 3.04 mol), (S)-(+)-2-amino-1-propanol (0.30 Kg, 3.95 mol) in toluene (6.50 L) was heated to reflux overnight. The reaction mixture was cooled to room temperature and DCM (6.5 L) and water (1.30 L) were added and the phases allowed to separate. Sodium triacetoxyborohydride (0.96 Kg, 4.56 mol) was added to the organic layer, followed by propionaldehyde (0.48 L, 6.68 mol) and glacial acetic acid (0.17 L, 3.04 mol) dropwise maintaining the temperature below 30° C. The reaction mixture was stirred at room temperature for 1 hour before quenching with water (1.20 L) and an aqueous solution of potassium carbonate (1.00 Kg in 3.23 Kg water) and the phases were allowed to separate. The aqueous phase was extracted with DCM (1.20 L) and the combined organic phases washed with water (0.60 L), water (0.30 L) and concentrated in vacuo. Yield 89% (0.89 Kg, the material was isolated in approximately 70% purity) δH (CDCl3, 300 MHz) 0.8-1.0 (6H, m), 1.50-1.70 (2H, m), 2.10 (6H, s), 2.50-3.15 (5H, m), 3.50 (2H, dd), 4.80 (1H, dd), 5.90 (2H, s), 7.20 (1H, m), 7.80-7.90 (1H, m), 8.60 (1H, m) ppm. MS m/z 332 (MH+). The intermediate amine was characterised as δH (CDCl3, 300 MHz) 1.10 (3H, t), 2.10 (6H, s), 2.7-3.2 (3H, m), 3.45 (1H, m), 3.70 (H, dd), 4.85 (1H, m), 5.90 (2H, s), 7.20 (1H, d), 7.90 (1H, dd), 8.60 (1H, d) ppm. MS m/z 290 (MH+).

Source