Aluminium lithium hydride → HCID 57657257, compound

HRID 244887Notes

Reaction equation

HRID 244887 reaction equation
[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH2:22][CH3:23])[N:14]([CH2:15][C:16]([OH:19])([CH3:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([CH2:24][CH2:25][C:26](OCC)=[O:27])=[CH:5][C:4]=2[N:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[NH2:1][C:2]1[C:11]2[N:12]=[C:13]([CH2:20][O:21][CH2:22][CH3:23])[N:14]([CH2:15][C:16]([OH:19])([CH3:17])[CH3:18])[C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([CH2:24][CH2:25][CH2:26][OH:27])=[CH:5][C:4]=2[N:3]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydride2×HCID 69078596HCID 69078596, compound

Product 1

HCID 57657257HCID 57657257, compoundYield 89.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A round bottom flask, equipped with a stir bar, was charged with ethyl 3-[4-amino-2-(ethoxymethyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]propanoate (1.0 g, 2.4 mmol) and anhydrous tetrahydrofuran (20 mL). The reaction mixture was cooled in an ice bath. Lithium aluminum hydride (92 mg, 2.4 mmol) was added in one portion. After 2 hours additional lithium aluminum hydride (92 mg, 2.4 mmol) was added in one portion. The ice bath was removed and the reaction mixture was allowed to warm to ambient temperature. The reaction was quenched by successive dropwise addition of water (1 mL), 10% sodium hydroxide solution (1 mL) and water (3 mL). The reaction mixture was maintained at ambient temperature for 18 hours and then diluted with diethyl ether and water. The fractions were separated and the aqueous fraction was extracted with diethyl ether (3×25 mL). All of the organic fractions were combined and then concentrated to dryness under reduced pressure. Purification by chromatography using a HORIZON HPFC system (silica cartridge, 0-20% CMA/chloroform) provided 0.8 g of 3-[4-amino-2-(ethoxymethyl)-1-(2-hydroxy-2-methylpropyl)-1H-imidazo[4,5-c]quinolin-7-yl]propan-1-ol as a white crystalline solid, mp 177-178° C.

Workup

  1. customA round bottom flask, equipped with a stir bar
  2. temperatureThe reaction mixture was cooled in an ice bath
  3. customThe ice bath was removed
  4. customThe reaction was quenched by successive dropwise addition of water (1 mL), 10% sodium hydroxide solution (1 mL) and water (3 mL)
  5. temperatureThe reaction mixture was maintained at ambient temperature for 18 hours
  6. additiondiluted with diethyl ether and water
  7. customThe fractions were separated
  8. extractionthe aqueous fraction was extracted with diethyl ether (3×25 mL)
  9. concentrationconcentrated to dryness under reduced pressure
  10. customPurification by chromatography

Sources & evidence

ORD record
ord-b994f4ec1d624e44a275f53e354b3c67
Source dataset
uspto-grants-2014_02
Patent number
US08658666B2

Reaction notes

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