2-Amino-5-methylpyridine → HCID 57504692, compound

HRID 1098236Notes

Reaction equation

HRID 1098236 reaction equation
C[Al](C)C.[CH3:5][C:6]1[CH:7]=[CH:8][C:9]([NH2:12])=[N:10][CH:11]=1.[Si:13]([O:20][C@@H:21]([CH3:31])[CH2:22][O:23][CH2:24][C@H:25]([OH:30])[C:26](OC)=[O:27])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]>C1(C)C=CC=CC=1>[Si:13]([O:20][C@@H:21]([CH3:31])[CH2:22][O:23][CH2:24][C@H:25]([OH:30])[C:26]([NH:12][C:9]1[CH:8]=[CH:7][C:6]([CH3:5])=[CH:11][N:10]=1)=[O:27])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 153482-Amino-5-methylpyridineHCID 16682925TrimethylaluminumHCID 59279520(S)-methyl 3-((S)-2-(tert-butyldimethylsilyloxy)propoxy)-2-hydroxypropanoate

Product 1

HCID 57504692HCID 57504692, compoundYield 78.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent3×

Conditions

Temperature
0 °C

Procedure

Trimethylaluminium (1.966 mL, 3.93 mmol) was added slowly to 5-methylpyridin-2-amine (0.407 g, 3.76 mmol) in toluene (20 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes. (S)-methyl 3-((S)-2-(tert-butyldimethylsilyloxy)propoxy)-2-hydroxypropanoate (Intermediate AS3) (1 g, 3.42 mmol) in toluene (4 mL) was added and the reaction was allowed to warm to room temperature and then heated at reflux for 4 hours (a further 5ml toluene was added to aid stirring). The reaction mixture was concentrated in vacuo. The residue was neutralised with citric acid (1M, aq) and then diluted with water and extracted with EtOAc. The combined organics were dried (MgSO4) and evaporated to afford the product (0.994 g) which was used without further purification. 1H NMR (400 MHz, CDCl3) δ 0.07 (6H, d), 0.88 (9H, s), 1.15 (3H, d), 2.30 (3H, s), 2.79-3.11 (1H, m), 3.39-3.51 (2H, m), 3.80-3.91 (2H, m), 3.94-4.03 (1H, m), 4.31-4.36 (1H, m), 7.49-7.56 (1H, m), 8.09-8.16 (2H, m), 9.20 (1H, s); m/z (ES+) (M+H)+=369.52; HPLC tR=2.73 min.

Workup

  1. temperatureto warm to room temperature
  2. temperatureheated
  3. additionwas added to aid
  4. stirringstirring)
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. additiondiluted with water
  7. extractionextracted with EtOAc
  8. dry with materialThe combined organics were dried (MgSO4)
  9. customevaporated

Sources & evidence

ORD record
ord-c83acd96e23b4bebaa46059e6d09ebc2
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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