Potassium Iodide → Methyl 4-[(4E)-3-[4-(methoxycarbonyl)benzyl]-5-(2-{[5-(3-methyl-2-oxotetrahydropyrimidin-1(2H)-yl)pentyl]oxy}phenyl)pent-4-en-1-yl]benzoate

HRID 1512218Notes

Reaction equation

HRID 1512218 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][NH:4][C:3]1=[O:8].[H-].[Na+].Cl[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][O:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1/[CH:24]=[CH:25]/[CH:26]([CH2:39][C:40]1[CH:45]=[CH:44][C:43]([C:46]([O:48][CH3:49])=[O:47])=[CH:42][CH:41]=1)[CH2:27][CH2:28][C:29]1[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][CH:30]=1.[I-].[K+].[Cl-].[NH4+]>CN(C=O)C>[CH3:49][O:48][C:46]([C:43]1[CH:44]=[CH:45][C:40]([CH2:39][CH:26](/[CH:25]=[CH:24]/[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=2[O:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][N:4]2[CH2:5][CH2:6][CH2:7][N:2]([CH3:1])[C:3]2=[O:8])[CH2:27][CH2:28][C:29]2[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][CH:30]=2)=[CH:41][CH:42]=1)=[O:47]

Participants

7

Reactant 5

HCID 4875Potassium IodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 128677481-Methyltetrahydropyrimidin-2(1H)-oneHCID 59437417Methyl 4-{(4E)-5-{2-[(5-chloropentyl)oxy]phenyl}-3-[4-(methoxycarbonyl)benzyl]pent-4-en-1-yl}benzoate

Product 1

HCID 59437423Methyl 4-[(4E)-3-[4-(methoxycarbonyl)benzyl]-5-(2-{[5-(3-methyl-2-oxotetrahydropyrimidin-1(2H)-yl)pentyl]oxy}phenyl)pent-4-en-1-yl]benzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 36.4 mg (0.319 mmol) of 1-methyltetrahydropyrimidin-2-one [CAS Reg. No. 10166-54-8] is initially charged in 1.5 ml of dry DMF, and 13.1 mg (0.328 mmol) of sodium hydride (60% in paraffin oil) are added. The mixture is stirred at room temperature for 45 min. The reaction solution is then cooled to 0° C. and a solution of 50 mg (0.091 mmol) of methyl 4-{(4E)-5-{2-[(5-chloropentyl)oxy]phenyl}-3-[4-(methoxycarbonyl)benzyl]pent-4-en-1-yl}benzoate (racemate; Example 32A) in 1.5 ml of dry DMF is added. This is followed by the addition of 1.5 mg (0.9 μmol) of potassium iodide. The mixture is stirred at room temperature for 1.5 h. The reaction solution is then carefully poured into 15 ml of ice-cold 10% strength ammonium chloride solution. The mixture is extracted twice with dichloromethane. The combined organic phases are dried over sodium sulfate, filtered and concentrated. This gives 47 mg (0.075 mmol, 82% of theory) of a colorless oil which is reacted without further purification.

Workup

  1. temperatureThe reaction solution is then cooled to 0° C.
  2. stirringThe mixture is stirred at room temperature for 1.5 h
  3. extractionThe mixture is extracted twice with dichloromethane
  4. dry with materialThe combined organic phases are dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThis gives 47 mg (0.075 mmol, 82% of theory) of a colorless oil which is reacted without further purification

Sources & evidence

ORD record
ord-1dc2971d83654a3b931ea9aa5459c704
Source dataset
uspto-grants-2012_07
Patent number
US08217063B2

Reaction notes

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