Aluminium lithium hydride → HCID 57781141, compound

HRID 1690766Notes

Reaction equation

HRID 1690766 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])[N:12]([CH3:21])[C:11]2([CH3:23])[CH3:22])[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])[N:12]([CH3:21])[C:11]2([CH3:23])[CH3:22])[CH:7]=[N:8][CH:9]=1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 57781146HCID 57781146, compound

Product 1

HCID 57781141HCID 57781141, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-(2,3,3-trimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinolin-4-yl)-3H-imidazole-4-carboxylic acid methyl ester (190 mg, 0.367 mmol) in THF (5.5 mL) at −25° C. is added lithium aluminum hydride (18 mg, 0.48 mmol). The reaction is permitted to warm to 0° C. over 2 h and the reaction is stirred for an additional 30 min at 0° C. After a total of 2.5 h the reaction is quenched at 0° C. by the consecutive addition of 9:1 THF/H2O (0.225 mL), 2M aqueous NaOH (0.090 mL), and H2O (0.170 mL). The reaction is warmed to room temperature and diluted with THF (2.0 mL). After addition of MgSO4 (250 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 in vacuo. The resulting residue is purified by silica gel flash chromatography (dichloromethane-methanol, 49:1 to 9:1) to afford 4-(5-hydroxymethyl-imidazol-1-yl)-2,3,3-trimethyl-3,4-dihydro-2H-isoquinolin-1-one as a colorless foam. High resolution mass spectrum (ES+) m/z 286.1547 [(M+H)+; calculated for C16H20N3O2: 286.1556]; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.22 (s, 3 H), 1.36 (s, 3 H), 2.12 (br. s, 1 H), 3.11 (s, 3 H), 4.65-4.95 (m, 2 H), 5.33 (s, 1 H), 6.95 (s, 1 H), 7.31-7.36 (m, 1 H), 7.37 (s, 1 H), 7.43-7.54 (m, 2 H), 8.18-8.25 (m, 1 H).

Workup

  1. customAfter a total of 2.5 h the reaction is quenched at 0° C. by the consecutive addition of 9:1 THF/H2O (0.225 mL), 2M aqueous NaOH (0.090 mL), and H2O (0.170 mL)
  2. temperatureThe reaction is warmed to room temperature
  3. additiondiluted with THF (2.0 mL)
  4. additionAfter addition of MgSO4 (250 mg)
  5. stirringthe heterogeneous mixture is stirred for 15 min
  6. filtrationfiltered through a pad of Celite
  7. washThe pad of Celite is washed with ethyl acetate
  8. concentrationthe combined filtrate is concentrated in vacuo
  9. customThe resulting residue is purified by silica gel flash chromatography (dichloromethane-methanol, 49:1 to 9:1)

Sources & evidence

ORD record
ord-76be8f82c0a24e5694de272dddb93207
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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