Ethyl 2-(6-aminopyridin-3-yl)acetate → Benzyl 2-(6-aminopyridin-3-yl)acetate

HRID 655676Notes

Reaction equation

HRID 655676 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=1>C(O)C1C=CC=CC=1.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH2:12][C:13]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[O:10])=[CH:4][CH:3]=1

Participants

4

Reactant 1

HCID 67143734Ethyl 2-(6-aminopyridin-3-yl)acetate

Product 1

HCID 59411185Benzyl 2-(6-aminopyridin-3-yl)acetate

Reagents, catalysts & solvents 2

HCID 76524Titanium tetraethoxideCatalystHCID 244Benzyl AlcoholSolvent

Conditions

Temperature
110 °C

Procedure

Ethyl 2-(6-aminopyridin-3-yl)acetate (described in WO 2009/091014) (1.5 g) was dissolved in benzyl alcohol (10 mL). Titanium(IV) ethoxide (1.74 mL) was added and the reaction was heated to 110° C. for 16 hours. The reaction was cooled to room temperature and quenched with 1N HCl. This mixture was basified with saturated sodium bicarbonate and extracted three times with ethyl acetate. The combined organics were dried over MgSO4, filtered, and concentrated. Purification by column chromatography, eluting with a gradient of 30-100% ethyl acetate in heptane, afforded the title compound Intermediate (5b) (1.04 g, 51% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 3.51 (2 H), 4.37 (2 H), 5.11 (2 H), 6.46 (1 H), 7.27-7.41 (6 H), 7.95 (1H). m/z 243.4 (M+H)+.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customquenched with 1N HCl
  3. extractionextracted three times with ethyl acetate
  4. dry with materialThe combined organics were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by column chromatography
  8. washeluting with a gradient of 30-100% ethyl acetate in heptane

Sources & evidence

ORD record
ord-4da6d4af34914f82bf8f84ee13483b86
Source dataset
uspto-grants-2011_12
Patent number
US08071606B2

Reaction notes

Loading…