Sodium hydride → HCID 69706416, compound

HRID 1359592Notes

Reaction equation

HRID 1359592 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][C:5]=1[I:12].Br/[C:14](=[CH:19]\[CH3:20])/[C:15]([O:17][CH3:18])=[O:16].CN1C(=O)N(C)CCC1>C1COCC1>[C:8]([C:7]1[CH:10]=[CH:11][C:4]([O:3][CH2:20][CH:19]=[CH:14][C:15]([O:17][CH3:18])=[O:16])=[C:5]([I:12])[CH:6]=1)#[N:9]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 637257117642-18-1HCID 109558154-Hydroxy-3-iodobenzonitrile

Product 1

HCID 69706416HCID 69706416, compoundYield 73.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
55 °C

Procedure

To a cooled (0° C.) suspension of NaH (1.5 g of 60% suspension in mineral oil, 38 mmol) in THF (80 mL) was added a solution comprised of 4-hydroxy-3-iodo-benzonitrile (8.4 g, 34 mmol) (reference example 12), methyl bromo-crotonate (6.65 mL tech. grade, approx. 51 mmol) and DMPU (10 mL) in THF (20 mL). On complete addition, the cold bath was removed and replaced with an oil bath. The reaction mixture was heated to 55° C. and stirred at this temperature for 4.5 hr, cooled to room temperature and acidified with 2M aqueous HCl. The mixture was then diluted with ethyl acetate, washed sequentially with water and brine, dried over MgSO4 and concentrated. The residue was triturated with hexane several times, leaving 8.6 g of the title compound as a solid. 1H NMR (CDCl3) d 3.78 (s, 3H), 4.80 (dd, J=4, 1 Hz, 1H), 6.35 (dt, J=16, 1 Hz, 1H), 6.79 (d, J=8 Hz, 1H), 7.05 (dt, J=16, 4 Hz, 1H), 7.60 (dd, J=8, 1 Hz, 1H), 8.06 (d, J=1 Hz, 1H). MS (EI) m/z 343 (M)+.

Workup

  1. temperatureTo a cooled
  2. additionwas added a solution
  3. additionOn complete addition
  4. customthe cold bath was removed
  5. customreplaced with an oil bath
  6. temperaturecooled to room temperature
  7. additionThe mixture was then diluted with ethyl acetate
  8. washwashed sequentially with water and brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated
  11. customThe residue was triturated with hexane several times

Sources & evidence

ORD record
ord-9d9d29d55f06417fb279d314c9826b61
Source dataset
uspto-grants-2003_07
Patent number
US06599918B2

Reaction notes

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