Tetrahydrofuran → HCID 66619387, compound

HRID 417099Notes

Reaction equation

HRID 417099 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.[H-].[Na+].Br[CH:19]([CH2:23][CH2:24][Br:25])[C:20]([O-:22])=[O:21].O1CCC[CH2:27]1>>[CH3:27][O:22][C:20](=[O:21])[CH:19]([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)[CH2:23][CH2:24][Br:25]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 21193804HCID 21193804, compoundHCID 425530416-(Benzyloxy)pyridin-3-ol

Product 1

HCID 66619387HCID 66619387, compoundYield 59%

Conditions

Temperature
0 °C

Procedure

To an ice-cold solution of 0.5 g (2.5 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 portion wise. After vigorous gas evolution had ceased, the reaction mixture was stirred for another 20 min. at 0° C. and then 0.44 mL (3.1 mmol) 2,4-dibromobutyrate (commercially available) were added dropwise. The light brown suspension was stirred for 23 h at room temperature and then poured onto 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. To the filtrate silica gel was added and the slurry evaporated. The resulting solid was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 70:30) to give the product as a colorless oil (59%). MS (Turbo Spray): m/z=382.1 [M+H].

Workup

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

Sources & evidence

ORD record
ord-0b3588b273524517b209ce3d87adacb9
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Reaction notes

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