Sodium hydride → Methyl 4-[(4E)-3-[4-(methoxycarbonyl)benzyl]-5-(2-{[5-(2-methyl-3-oxomorpholin-4-yl)pentyl]-oxy}phenyl)pent-4-en-1-yl]benzoate

HRID 1512217Notes

Reaction equation

HRID 1512217 reaction equation
[CH3:1][CH:2]1[O: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.[Cl-].[NH4+]>CN(C=O)C>[CH3:49][O:48][C:46]([C:43]1[CH:42]=[CH:41][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][O:7][CH: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:45][CH:44]=1)=[O:47]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 134406282-Methyl-3-morpholinoneHCID 59437417Methyl 4-{(4E)-5-{2-[(5-chloropentyl)oxy]phenyl}-3-[4-(methoxycarbonyl)benzyl]pent-4-en-1-yl}benzoate

Product 1

HCID 59437418Methyl 4-[(4E)-3-[4-(methoxycarbonyl)benzyl]-5-(2-{[5-(2-methyl-3-oxomorpholin-4-yl)pentyl]-oxy}phenyl)pent-4-en-1-yl]benzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 66 mg (0.57 mmol) of 2-methylmorpholin-3-one [CAS Reg. No. 100636-23-5] is initially charged in 4.5 ml of dry DMF, and 23.6 mg (0.196 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 90 mg (0.163 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. 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 103 mg (0.57 mmol, 100% 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 103 mg (0.57 mmol, 100% of theory) of a colorless oil which is reacted without further purification

Sources & evidence

ORD record
ord-9173130447444277896a3427ab4f789f
Source dataset
uspto-grants-2012_07
Patent number
US08217063B2

Reaction notes

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