Ethanol → HCID 67546399, compound

HRID 386445Notes

Reaction equation

HRID 386445 reaction equation
CCO.C(Cl)(=O)C.[CH2:8]([O:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][CH:24]([OH:27])[C:25]#[N:26])=[CH:18][CH:17]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.N[C:29]1[C:34]([OH:35])=[CH:33][CH:32]=[CH:31][N:30]=1>C(Cl)(Cl)Cl>[CH2:8]([O:15][C:16]1[CH:17]=[CH:18][C:19]([CH2:22][CH2:23][CH:24]([C:25]2[O:35][C:34]3[C:29]([N:26]=2)=[N:30][CH:31]=[CH:32][CH:33]=3)[OH:27])=[CH:20][CH:21]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 6367Acetyl chlorideHCID 281142-Amino-3-HydroxypyridineHCID 86645814HCID 86645814, compound

Product 1

HCID 67546399HCID 67546399, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

A mixture of anhydrous EtOH (3.6 mL) and CHCl3 (4.0 mL) at 0° C. was treated with acetyl chloride (3.4 mL, 47.6 mmol, 16.2 equiv) and was stirred for 20 min. A solution of 4-(4-(benzyloxy)phenyl)-2-hydroxybutanenitrile (S50, 750 mg, 2.94 mmol, 1 equiv) in 9 mL of CHCl3 was added dropwise and the reaction was stirred for 20 h at 25° C. The reaction mixture was concentrated and the crude product was dissolved in anhydrous EtOH. 2-Amino-3-hydroxypyridine (370 mg, 3.36 mmol, 1.1 equiv) was added and the reaction mixture was warmed at reflux overnight. Concentration followed by column chromatography (SiO2, 2.5×8 cm, 0-4% MeOH—CHCl3 gradient) afforded S51 (130 mg, 0.36 mmol, 13%) as a tan oil: 1H NMR (CDCl3, 600 MHz) 8.52 (d, 1H, J=4.8 Hz), 7.78 (d, 1H, J=7.9 Hz), 7.43 (d, 2H, J=7.0 Hz), 7.39 (t, 2H, J=7.9 Hz), 7.34-7.31 (m, 1H), 7.28-7.26 (m, 1H), 7.14 (d, 2H, J=8.3 Hz), 6.87 (d, 2H, J=8.3 Hz), 5.07-5.00 (m, 1H), 5.00 (s, 2H), 2.84-2.81 (m, 2H), 2.36-2.30 (m, 2H); 13C NMR (CDCl3, 150 MHz) 157.0, 154.6, 146.1, 143.0, 137.0, 133.0 (2C), 129.4, 128.5, 127.8, 127.4, 120.2, 118.8, 114.7, 69.9, 67.0, 36.9, 30.1; IR (film) νmax 3380, 2926, 1665, 1612, 1557, 1511, 1454, 1410, 1382, 1239, 1177, 1092, 1026, 831, 785, 737, 700 cm−1.

Workup

  1. stirringthe reaction was stirred for 20 h at 25° C
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionthe crude product was dissolved in anhydrous EtOH
  4. temperaturethe reaction mixture was warmed
  5. temperatureat reflux overnight
  6. concentrationConcentration
  7. customafforded S51 (130 mg, 0.36 mmol, 13%) as a tan oil

Sources & evidence

ORD record
ord-03c19f7aa0a741b9af41df29337478f8
Source dataset
uspto-grants-2013_02
Patent number
US08372823B2

Reaction notes

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