Ammonia → HCID 17982946, compound

HRID 1268891Notes

Reaction equation

HRID 1268891 reaction equation
[Si]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH3:15])=[N:13][CH:14]=1)(C(C)(C)C)(C)C.[Li+].CC([N-]C(C)C)C.[CH2:24]([O:31][C:32]1[CH:33]=[C:34]([CH:37]=[C:38]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:39]=1)[CH:35]=[O:36])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.Cl.N>C1COCC1.O>[CH2:41]([O:40][C:38]1[CH:37]=[C:34]([CH:35]([OH:36])[CH2:15][C:12]2[N:13]=[CH:14][C:9]([OH:8])=[CH:10][CH:11]=2)[CH:33]=[C:32]([O:31][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:39]=1)[C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1

Participants

8

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 5613513,5-DibenzyloxybenzaldehydeHCID 2724682Lithium diisopropylamideHCID 45117511HCID 45117511, compound

Product 1

HCID 17982946HCID 17982946, compoundYield 98%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of 5-{[tert-butyl(dimethyl)silyl]oxy}-2-methyl pyridine (1.20 g) in anhydrous THF (15 ml) under nitrogen and at −78° C. was added LDA (3.22 ml), and the solution stirred at −78° C. for 1 hour. 3,5 dibenzyloxy-benzaldehyde (2.05 g) was then added dropwise as a solution in THF, and the reaction mixture allowed to warm to ambient temperature over 1 hour. Water (20 ml) was added and the resulting mixture extracted with ethyl acetate (3×30 ml). The extracts were combined, washed with brine (20 ml), dried (MgSO4) and evaporated to give a gum. This was dissolved in THF (10 ml) and concentrated hydrochloric acid (10 ml) added. The mixture was stirred at ambient temperature for 3 hours, cooled to 0° C. and taken to pH 8.5 with concentrated ammonia solution. The mixture was diluted with water (50 ml) and extracted with ethyl acetate (3×100 ml). The extracts were combined, dried (MgSO4) and evaporated to leave an oil which was purified by MPLC on silica, eluting with 60–100% ethyl acetate in hexane to give 6-{2-[3,5-bis(benzyloxy)phenyl]-2-hydroxyethyl}pyridin-3-ol (2.25 g) as a glass, m/z 428 (M+H)+.

Workup

  1. temperatureto warm to ambient temperature over 1 hour
  2. extractionthe resulting mixture extracted with ethyl acetate (3×30 ml)
  3. washwashed with brine (20 ml)
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customto give a gum
  7. stirringThe mixture was stirred at ambient temperature for 3 hours
  8. temperaturecooled to 0° C.
  9. extractionextracted with ethyl acetate (3×100 ml)
  10. dry with materialdried (MgSO4)
  11. customevaporated
  12. customto leave an oil which
  13. customwas purified by MPLC on silica
  14. washeluting with 60–100% ethyl acetate in hexane

Sources & evidence

ORD record
ord-110151dcde2a43ea88ef2c35bf0ba6a4
Source dataset
uspto-grants-2007_04
Patent number
US07199140B2

Reaction notes

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