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

HRID 1781987Notes

Reaction equation

HRID 1781987 reaction equation
[CH3:1][C:2]1[N:3]([C:8]2[N:13]=[CH:12][C:11]([CH:14]([OH:21])[CH2:15][NH:16][C@@H:17]([CH3:20])[CH2:18][OH:19])=[CH:10][CH:9]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1.C(O[BH-](O[C:32](=O)[CH3:33])OC(=O)C)(=O)C.[Na+].[CH2:36](Cl)Cl>>[CH3:7][C:4]1[N:3]([C:8]2[N:13]=[CH:12][C:11]([CH:14]([OH:21])[CH2:15][N:16]([CH2:36][CH2:32][CH3:33])[C@@H:17]([CH3:20])[CH2:18][OH:19])=[CH:10][CH:9]=2)[C:2]([CH3:1])=[CH:6][CH:5]=1

Participants

4

Reactant 3

HCID 6344Dichloromethane3×HCID 5049666Sodium triacetoxyborohydrideHCID 11551021(2S)-2-[{(RS)-2-[6-(2,5-dimethyl-1H-pyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl} amino]propan-1-ol

Product 1

HCID 59645265(2S)-2-[{(RS)-2-[6-(2,5-dimethyl-1H-pyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl}propylamino]propan-1-olYield 100%

Conditions

Temperature
20 °C

Procedure

Propioanaldehyde (5.02 Kg, 86.4 mol) was added over 10 minutes to a solution of (2S)-2-[{(RS)-2-[6-(2,5-dimethyl-1H-pyrrol-1-yl)pyridin-3-yl]-2-hydroxyethyl} amino]propan-1-ol (22.7 Kg, 78.6 mol) in DCM (123 L) at 20° C. The resulting solution was stirred at 20° C. for 2 hours and then allowed to settle before adding it to a suspension of sodium triacetoxyborohydride (25.8 Kg, 122 mol) in DCM (123 L) over 90 minutes maintaining the temperature below 30° C. The reaction mixture was stirred at 20° C. for 1 hour before quenching with an aqueous solution of potassium carbonate (36.4 Kg in 136 L of water) and the phases were allowed to separate. The organic phase was washed with water (2×23 L). The equipment was set for distillation and DCM (190 L) was removed by distillation to give a final volume of 45 litres. The mixture was cooled to 20° C. Yield 100% (51.1 Kg, 50.9% w/w in DCM). 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+).

Workup

  1. additionbefore adding it
  2. temperaturemaintaining the temperature below 30° C
  3. stirringThe reaction mixture was stirred at 20° C. for 1 hour
  4. custombefore quenching with an aqueous solution of potassium carbonate (36.4 Kg in 136 L of water)
  5. customto separate
  6. washThe organic phase was washed with water (2×23 L)
  7. distillationThe equipment was set for distillation and DCM (190 L)
  8. customwas removed by distillation
  9. customto give a final volume of 45 litres
  10. temperatureThe mixture was cooled to 20° C

Sources & evidence

ORD record
ord-930a6bc0fb78413f84726922de9c8a63
Source dataset
uspto-grants-2009_03
Patent number
US07498329B2

Reaction notes

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