Sodium hydride → t-Butyl [[2-(5-Bromo-1-naphthalenyl)-5-cyano-6-[(1-naphthalenyl)methyl]-4-pyrimidinyl]oxy]acetate

HRID 2232061Notes

Reaction equation

HRID 2232061 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][CH:8]=[C:9]2[C:14]1[NH:15][C:16](=[O:33])[C:17]([C:31]#[N:32])=[C:18]([CH2:20][C:21]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:24]=[CH:23][CH:22]=2)[N:19]=1.Br[CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37]>CN(C=O)C>[Br:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][CH:8]=[C:9]2[C:14]1[N:15]=[C:16]([O:33][CH2:35][C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[C:17]([C:31]#[N:32])=[C:18]([CH2:20][C:21]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:24]=[CH:23][CH:22]=2)[N:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 1358476532-(5-Bromo-1-naphthalenyl)-1,6-dihydro-4-[(1-naphthalenyl)methyl]-6-oxo-5-pyrimidinecarbonitrile

Product 1

HCID 86742536t-Butyl [[2-(5-Bromo-1-naphthalenyl)-5-cyano-6-[(1-naphthalenyl)methyl]-4-pyrimidinyl]oxy]acetateYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred suspension of NaH (60% suspension in mineral oil, washed with hexane, 0.64 g, 16.1 mmol) in DMF (25 mL) was added a solution of 2-(5-bromo-1-naphthalenyl)-1,6-dihydro-4-[(1-naphthalenyl)methyl]-6-oxo-5-pyrimidinecarbonitrile (prepared in Step 3) (5.0 g, 10.7 mmol) in DMF (100 mL) at room temperature. After 30 minutes, t-butyl bromoacetate was added and stirring was continued for 18 hours. The reaction was quenched by the addition of water (10 mL) and the resulting mixture was partitioned between chloroform (200 mL) and water. The aqueous layer was extracted with chloroform (2×100 mL) and the combined organic layers were washed with water, brine, and dried (Na2SO4). The mixture was filtered through a short plug of Florosil and concentrated in vacuo to give a yellow solid (5.8 g, 48%). Recrystallization from acetonitrile/DMF gave 3.0 g of product which was used without further purification.

Workup

  1. waitwas continued for 18 hours
  2. customThe reaction was quenched by the addition of water (10 mL)
  3. customthe resulting mixture was partitioned between chloroform (200 mL) and water
  4. extractionThe aqueous layer was extracted with chloroform (2×100 mL)
  5. washthe combined organic layers were washed with water, brine
  6. dry with materialdried (Na2SO4)
  7. filtrationThe mixture was filtered through a short plug of Florosil
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d5916836e8f446e0930a09586a64b95f
Source dataset
uspto-grants-1988_11
Patent number
US04786640

Reaction notes

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