2-Amino-5-methylpyridine → HCID 57504669, compound

HRID 1098247Notes

Reaction equation

HRID 1098247 reaction equation
C[Al](C)C.[CH3:5][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>[OH:13][C@@H:14]([CH2:19][O:20][C@H:21]([CH3:34])[CH2:22][O:23][Si:24]([CH:28]([CH3:30])[CH3:29])([CH:31]([CH3:33])[CH3:32])[CH:25]([CH3:26])[CH3:27])[C:15]([NH:12][C:9]1[CH:8]=[CH:7][C:6]([CH3:5])=[CH:11][N:10]=1)=[O:16]

Participants

5

Reactant 3

HCID 153482-Amino-5-methylpyridineHCID 16682925TrimethylaluminumHCID 59279456HCID 59279456, compound

Product 1

HCID 57504669HCID 57504669, compoundYield 65.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

Trimethylaluminium (2M in toluene) (8.97 ml, 17.94 mmol) was added to 5-methylpyridin-2-amine (1.940 g, 17.94 mmol) in toluene (70 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) (3.0 g, 8.97 mmol) in toluene (20 ml) was added and the reaction was allowed to warm to room temperature and then heated at reflux for 5 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 (50 mL) and extracted with EtOAc (2×100 mL). The combined organics were dried (MgSO4) filtered and evaporated. The crude product was purified by flash silica chromatography, eluting with 30 to 50% EtOAc in isohexane to afford the product (2.40 g, 65.2%). 1H NMR (400 MHz, CDCl3) δ 1.03-1.15 (24H, m), 2.29 (3H, s), 3.60-3.68 (3H, m), 3.82-3.86 (1H, m), 3.98-4.02 (1H, m), 4.14-4.15 (1H, m), 4.30-4.34 (1H, m), 7.49-7.52 (1H, m), 8.11-8.13 (2H, m), 9.14 (1H, s); m/z (ES+) (M+H)+=411.44; HPLC tR=3.46 min.

Workup

  1. temperatureto warm to room temperature
  2. temperatureheated
  3. temperatureat reflux for 5 hours
  4. temperatureto cool
  5. concentrationconcentrated in vacuo
  6. additiondiluted with water (50 mL)
  7. extractionextracted with EtOAc (2×100 mL)
  8. dry with materialThe combined organics were dried (MgSO4)
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude product was purified by flash silica chromatography
  12. washeluting with 30 to 50% EtOAc in isohexane

Sources & evidence

ORD record
ord-4df2e527de22436bb26fd167f96a4918
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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