Sodium hydride → (2S)-2-[1-(3-chloro-benzyl)-2-oxo-1,4-dihydro-2H-quinazolin-3-yl]-3-Methyl-butyric acid tert-butyl ester

HRID 602934Notes

Reaction equation

HRID 602934 reaction equation
[C:1]([O:5][C:6](=[O:22])[C@@H:7]([N:11]1[CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:13][C:12]1=[O:21])[CH:8]([CH3:10])[CH3:9])([CH3:4])([CH3:3])[CH3:2].[Cl:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH2:27]Br.[H-].[Na+]>CS(C)=O>[C:1]([O:5][C:6](=[O:22])[C@@H:7]([N:11]1[CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:13]([CH2:27][C:26]2[CH:29]=[CH:30][CH:31]=[C:24]([Cl:23])[CH:25]=2)[C:12]1=[O:21])[CH:8]([CH3:10])[CH3:9])([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 698381-(Bromomethyl)-3-chlorobenzeneHCID 66650119(2S)-3-Methyl-2-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-butyric acid tert-butyl ester

Product 1

HCID 53628862(2S)-2-[1-(3-chloro-benzyl)-2-oxo-1,4-dihydro-2H-quinazolin-3-yl]-3-Methyl-butyric acid tert-butyl esterYield 59%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a mixture of (2S)-3-methyl-2-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-butyric acid tert-butyl ester (633 mg, 2.08 mmol) and 3-chlorobenzyl bromide (470 mg, 2.29 mmol) in DMSO (10 mL) was added sodium hydride (75 mg, 1.87 mmol) and the reaction mixture was stirred at room temperature for 40 hours. To this reaction was then added sat. aq. NH4Cl and the mixture was extracted with ethyl acetate. The organic phase was dried (MgSO4), filtered and evaporated. The residue was purified by flash chromatography (hexane/ethyl acetate, 70/30) to afford the title compound as a colorless oil (477 mg, 59%). 1H NMR (400 MHz CDCl3) δ 0.99 (3H, d), 1.08 (3H, d), 1.48 (9H, s), 2.32 (1H, m), 4.42 (1H, d), 4.59-4.67 (2H, m), 5.05-5.19 (2H, m), 6.68 (1H, d), 6.97 (1H, t), 7.06-7.27 (6H, m).

Workup

  1. extractionadded sat. aq. NH4Cl and the mixture was extracted with ethyl acetate
  2. dry with materialThe organic phase was dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by flash chromatography (hexane/ethyl acetate, 70/30)

Sources & evidence

ORD record
ord-91c3f3c6254945f889e5942b514ae759
Source dataset
uspto-grants-2011_03
Patent number
US07906650B2

Reaction notes

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