2-Aminopyridine → (S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxy-N-(pyridin-2-yl)propanamide

HRID 1098229Notes

Reaction equation

HRID 1098229 reaction equation
C[Al](C)C.[N:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH2:11].[Si:12]([O:29][CH2:30][CH2:31][O:32][CH2:33][C@H:34]([OH:39])[C:35](OC)=[O:36])([C:25]([CH3:28])([CH3:27])[CH3:26])([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C1(C)C=CC=CC=1>[Si:12]([O:29][CH2:30][CH2:31][O:32][CH2:33][C@H:34]([OH:39])[C:35]([NH:11][C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][N:5]=1)=[O:36])([C:25]([CH3:28])([CH3:26])[CH3:27])([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 104392-AminopyridineHCID 16682925TrimethylaluminumHCID 59279512(S)-methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxypropanoate

Product 1

HCID 57504689(S)-3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxy-N-(pyridin-2-yl)propanamideYield 62.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

Trimethylaluminium (3.73 mL, 7.45 mmol) was added to pyridin-2-amine (0.701 g, 7.45 mmol) in toluene (6 ml) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 20 minutes. (S)-methyl 3-(2-(tert-butyldiphenylsilyloxy)ethoxy)-2-hydroxypropanoate (1.5 g, 3.73 mmol) (Intermediate AB3) in toluene (6 ml) was added and the reaction was allowed to warm to room temperature and then heated to 110 for 5 hours in a microwave. 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), filtered and evaporated. The crude product was purified by flash silica chromatography, eluting with 30 to 50% EtOAc in isohexane to afford the product (1.085 g, 62.7%). 1H NMR: (400 MHz, CDCl3) δ 1.05 (9H, t), 3.60-3.66 (2H, m), 3.67 (1H, d), 3.82-3.84 (2H d, m), 3.80-3.85 (2H, m), 4.33-4.35 (1H, m), 7.03-7.06 (1H, m), 7.35-7.68 (10H, m), 7.70 (1H, d), 8.22 (1H, d), 8.29-8.30 (1H, m),9.15 (1H, s); m/z (ES+) (M+H)+=465.42; HPLC tR=3.13 min.

Workup

  1. temperatureto warm to room temperature
  2. temperatureheated to 110 for 5 hours in a microwave
  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. 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-12aadae21f4b4b44bae4ddd5c4630c68
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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