Tetrahydrofuran → 2-(6-Benzyloxy-pyridin-3-yloxy)-2-methyl-propionic acid ethyl ester

HRID 417096Notes

Reaction equation

HRID 417096 reaction equation
[CH2:1]([O:8][C:9]1[N:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1CCCC1.[CH2:21]([O:23][C:24](=[O:29])[C:25](Br)([CH3:27])[CH3:26])[CH3:22]>O>[CH2:21]([O:23][C:24](=[O:29])[C:25]([O:15][C:12]1[CH:13]=[N:14][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:10][CH:11]=1)([CH3:27])[CH3:26])[CH3:22]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 425530416-(Benzyloxy)pyridin-3-ol

Product 1

HCID 666194512-(6-Benzyloxy-pyridin-3-yloxy)-2-methyl-propionic acid ethyl esterYield 38%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To an ice-cold solution of 0.5 g (2.48 mmol) 6-benzyloxy-3-hydroxypyridine (commercially available) in 5 mL tetrahydrofuran 0.12 g (2.7 mmol) sodium hydride (55% dispersion in mineral oil) was added in portions. After the vigorous gas evolution had ceased the reaction mixture was stirred for another 20 min., then 0.44 mL (3.0 mmol) ethyl-alpha-bromoisobutyrate (commercially available) were added dropwise. The light brown suspension was stirred for 23 h at room temperature and then poured into water. The aqueous phase was extracted three times with ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulfate and filtered. Silica gel was added to the filtrate and the slurry evaporated. The resulting solid is purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane:ethyl acetate (100:0 to 70:30) to give the product as a colorless oil (38%). MS (Turbo Spray): m/z=316.1 [M+H].

Workup

  1. stirringThe light brown suspension was stirred for 23 h at room temperature
  2. extractionThe aqueous phase was extracted three times with ethyl acetate
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. additionSilica gel was added to the filtrate
  7. customthe slurry evaporated
  8. customThe resulting solid is purified by silica gel chromatography
  9. washeluting with a gradient of heptane:ethyl acetate (100:0 to 70:30)

Sources & evidence

ORD record
ord-5c6b4d454c3f4d4cb9f6f496a49f95ed
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Reaction notes

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