2-Amino-5-fluoropyridine → HCID 57504745, compound

HRID 1098285Notes

Reaction equation

HRID 1098285 reaction equation
C[Al](C)C.[F:5][C:6]1[CH:7]=[CH:8][C:9]([NH2:12])=[N:10][CH:11]=1.[OH:13][C@@H:14]([CH2:19][O:20][C@H:21]([CH3:34])[CH2:22][O:23][Si:24]([CH:31]([CH3:33])[CH3:32])([CH:28]([CH3:30])[CH3:29])[CH:25]([CH3:27])[CH3:26])[C:15](OC)=[O:16]>C1(C)C=CC=CC=1>[F:5][C:6]1[CH:7]=[CH:8][C:9]([NH:12][C:15](=[O:16])[C@@H:14]([OH:13])[CH2:19][O:20][C@@H:21]([CH3:34])[CH2:22][O:23][Si:24]([CH:28]([CH3:30])[CH3:29])([CH:25]([CH3:26])[CH3:27])[CH:31]([CH3:32])[CH3:33])=[N:10][CH:11]=1

Participants

5

Reactant 3

HCID 27377012-Amino-5-fluoropyridineHCID 16682925TrimethylaluminumHCID 59279456HCID 59279456, compound

Product 1

HCID 57504745HCID 57504745, compoundYield 75.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

Trimethylaluminium (5.98 mL, 11.96 mmol) was added to 5-fluoropyridin-2-amine (1.340 g, 11.96 mmol) in toluene (20 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 20 minutes. (S)-Methyl 2-hydroxy-3-((R)-1-(triisopropylsilyloxy)propan-2-yloxy)propanoate (Intermediate AU5) (2 g, 5.98 mmol) in toluene (6 mL) was added and the reaction was allowed to warm to room temperature and then refluxed for 6 hours. The reaction mixture was allowed to cool and concentrated in vacuo. The residue was neutralised with citric acid (1M, aq) and then diluted with water (25 mL) and extracted with EtOAc (2×50 mL). The combined organics were washed with brine (20 mL), then dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 30 to 50% EtOAc in isohexane to afford the product (1.863 g, 75%).

Workup

  1. temperatureto warm to room temperature
  2. temperaturerefluxed for 6 hours
  3. temperatureto cool
  4. concentrationconcentrated in vacuo
  5. additiondiluted with water (25 mL)
  6. extractionextracted with EtOAc (2×50 mL)
  7. washThe combined organics were washed with brine (20 mL)
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customThe crude product was purified by flash silica chromatography
  11. washeluting with 30 to 50% EtOAc in isohexane

Sources & evidence

ORD record
ord-1a09126ccea64003b4b953cc1c9e1c74
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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