Aluminium lithium hydride → HCID 57781143, compound

HRID 1690767Notes

Reaction equation

HRID 1690767 reaction equation
C[O:2][C:3]([C:5]1[N:6]([CH:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13](=[O:20])[NH:12][C:11]2([CH3:22])[CH3:21])[CH:7]=[N:8][CH:9]=1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[OH:2][CH2:3][C:5]1[N:6]([CH:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13](=[O:20])[NH:12][C:11]2([CH3:22])[CH3:21])[CH:7]=[N:8][CH:9]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 57781144HCID 57781144, compound

Product 1

HCID 57781143HCID 57781143, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-(3,3-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinolin-4-yl)-3H-imidazole-4-carboxylic acid methyl ester (200 mg, 0.67 mmol) (Example 33c) in THF (20 mL) at −10° C. is added lithium aluminum hydride (56 mg, 1.47 mmol). After stirring for 5 min the reaction is placed at room temperature for 1 h, at which time the reaction is cooled to 0° C. and quenched by the consecutive addition of 9:1 THF/H2O (0.8 mL), 2M aqueous NaOH (0.92 mL), and H2O (0.6 mL). The reaction is then warmed to room temperature and diluted with THF (6 mL). After the addition of MgSO4 (900 mg), the heterogeneous mixture is stirred for 15 min and then filtered through a pad of Celite®. The pad of Celite® is washed with ethyl acetate and the combined filtrate is concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-hexanes-ethanol, 6.5:2.5:1 to 9:0.5:1.2) to furnish 4-(5-hydroxymethyl-imidazol-1-yl)-3,3-dimethyl-3,4-dihydro-2H-isoquinolin-1-one; MS (ESI) m/z 272.0 (M+H); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.11 (s, 3 H), 1.42 (s, 3 H), 2.25 (br. s., 1 H), 4.61-4.93 (m, 2 H), 5.40 (s, 1 H), 5.73 (br. s., 1 H), 6.96 (s, 1 H), 7.32-7.37 (m, 1 H), 7.38 (s, 1 H), 7.46-7.56 (m, 2 H), 8.15-8.26 (m, 1 H).

Workup

  1. waitis placed at room temperature for 1 h, at which time
  2. customquenched by the consecutive addition of 9:1 THF/H2O (0.8 mL), 2M aqueous NaOH (0.92 mL), and H2O (0.6 mL)
  3. temperatureThe reaction is then warmed to room temperature
  4. additiondiluted with THF (6 mL)
  5. additionAfter the addition of MgSO4 (900 mg)
  6. stirringthe heterogeneous mixture is stirred for 15 min
  7. filtrationfiltered through a pad of Celite®
  8. washThe pad of Celite® is washed with ethyl acetate
  9. concentrationthe combined filtrate is concentrated
  10. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-hexanes-ethanol, 6.5:2.5:1 to 9:0.5:1.2)

Sources & evidence

ORD record
ord-8534aff173e04283b89131a81ac773ef
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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