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

HRID 1781985Notes

Reaction equation

HRID 1781985 reaction equation
[CH3:1][C:2]1[N:3]([C:8]2[CH:13]=[CH:12][C:11]([CH:14]3[CH2:16][O:15]3)=[CH:10][N:9]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1.[NH2:17][C@@H:18]([CH3:21])[CH2:19][OH:20].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH:36](=O)[CH2:37][CH3:38].C(O)(=O)C>C1(C)C=CC=CC=1.O.C(Cl)Cl>[CH3:1][C:2]1[N:3]([C:8]2[N:9]=[CH:10][C:11]([CH:14]([OH:15])[CH2:16][N:17]([CH2:36][CH2:37][CH3:38])[C@@H:18]([CH3:21])[CH2:19][OH:20])=[CH:12][CH:13]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 527PropanalHCID 80307L-AlaninolHCID 5049666Sodium triacetoxyborohydrideHCID 220512242-(2,5-Dimethylpyrrol-1-yl)-5-oxiranylpyridine

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 89%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

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+).

Workup

  1. temperaturewas heated
  2. temperatureto reflux overnight
  3. customto separate
  4. temperaturedropwise maintaining the temperature below 30° C
  5. custombefore quenching with water (1.20 L)
  6. customto separate
  7. extractionThe aqueous phase was extracted with DCM (1.20 L)
  8. washthe combined organic phases washed with water (0.60 L), water (0.30 L)
  9. concentrationconcentrated in vacuo
  10. customYield 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

Sources & evidence

ORD record
ord-b710966a6568404d83990214ede4ffd5
Source dataset
uspto-grants-2009_03
Patent number
US07498329B2

Reaction notes

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