Aluminium lithium hydride → 5-bromo-1-(2,6-dichlorophenyl)-7-(hydroxymethyl)-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one

HRID 394107Notes

Reaction equation

HRID 394107 reaction equation
[Br:1][C:2]1[CH:11]=[C:10]([C:12](OC)=[O:13])[CH:9]=[C:8]2[C:3]=1[CH2:4][N:5]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)[C:6](=[O:24])[N:7]2[C:16]1[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][C:17]=1[Cl:23].[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[Br:1][C:2]1[CH:11]=[C:10]([CH2:12][OH:13])[CH:9]=[C:8]2[C:3]=1[CH2:4][N:5]([CH2:25][C:26]1[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=1)[C:6](=[O:24])[N:7]2[C:16]1[C:17]([Cl:23])=[CH:18][CH:19]=[CH:20][C:21]=1[Cl:22]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 22647942Methyl 5-bromo-1-(2,6-dichlorophenyl)-3-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate2×

Product 1

HCID 226479525-bromo-1-(2,6-dichlorophenyl)-7-(hydroxymethyl)-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of methyl 5-bromo-1-(2,6-dichlorophenyl)-3-(4-methoxybenzyl)-2-oxo-1,2,3,4-tetrahydroquinazoline-7-carboxylate (INTERMEDIATE 27)(2 g, 3.63 mmol) in anhydrous THF at 0° C. was added lithium aluminum hydride (1.0M in THF, 4.7 mL, 4.73 mmol) slowly. The reaction was stirred at 0° C. for 40 min, quenched with water slowly and diluted with methylene chloride. The mixture was filtered through celite and rinsed with methylene chloride. Removal of the solvent and subsequent purification by flash chromatography using 20% of acetone in hexane as eluent provided the 5-bromo-1-(2,6-dichlorophenyl)-7-(hydroxymethyl)-3-(4-methoxybenzyl)-3,4-dihydroquinazolin-2(1H)-one as a white solid. 1H NMR (CDCl3, 500 MHz): δ 3.83 (s, 3H), 4.49 (s, 2H), 4.50 (s, 2H), 4.69 (s, 2H), 5.98 (s, 1H), 6.92 (d, 2H, J=8.5 Hz), 7.23 (s, 1H), 7.36 (m, 3H), 7.52 (d, 2H, J=8.0 Hz). MS (API-ES+): 523 (M+H).

Workup

  1. customquenched with water slowly
  2. additiondiluted with methylene chloride
  3. filtrationThe mixture was filtered through celite
  4. washrinsed with methylene chloride
  5. customRemoval of the solvent and subsequent purification by flash chromatography

Sources & evidence

ORD record
ord-472402837b2547e797c45c7046c8c418
Source dataset
uspto-grants-2004_10
Patent number
US06809199B2

Reaction notes

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