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

HRID 1512212Notes

Reaction equation

HRID 1512212 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][C:2]1=[O:7].[H-].[Na+].Br[CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1/[CH:21]=[CH:22]/[CH:23]([CH2:36][C:37]1[CH:42]=[CH:41][C:40]([C:43]([O:45][CH3:46])=[O:44])=[CH:39][CH:38]=1)[CH2:24][CH2:25][C:26]1[CH:35]=[CH:34][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:28][CH:27]=1.[Cl-].[NH4+]>CN(C=O)C>[CH3:46][O:45][C:43]([C:40]1[CH:39]=[CH:38][C:37]([CH2:36][CH:23](/[CH:22]=[CH:21]/[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[O:14][CH2:13][CH2:12][CH2:11][N:1]2[CH2:6][CH2:5][O:4][CH2:3][C:2]2=[O:7])[CH2:24][CH2:25][C:26]2[CH:35]=[CH:34][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:28][CH:27]=2)=[CH:42][CH:41]=1)=[O:44]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 669533-MorpholinoneHCID 59437413Methyl 4-{(4E)-5-[2-(3-bromopropoxy)phenyl]-3-[4-(methoxycarbonyl)benzyl]pent-4-en-1-yl}benzoate

Product 1

HCID 59437426Methyl 4-[(4E)-3-[4-(methoxycarbonyl)benzyl]-5-{2-[3-(3-oxomorpholin-4-yl)propoxy]phenyl}pent-4-en-1-yl]benzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 0.175 g (1.73 mmol) of morpholin-3-one [CAS Reg. No. 109-11-5] is initially charged in 6 ml of dry DMF, and 71 mg (1.78 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 0.28 g (0.495 mmol) of methyl 4-{(4E)-5-[2-(3-bromopropoxy)phenyl]-3-[4-(methoxycarbonyl)benzyl]pent-4-en-1-yl}benzoate (Example 22A) in 3 ml of dry DMF is added. The mixture is stirred at room temperature for 1 h. The reaction solution is then carefully poured into 50 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 0.29 g (0.495 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 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 0.29 g (0.495 mmol, 100% of theory) of a colorless oil which is reacted without further purification

Sources & evidence

ORD record
ord-8be8bcf951404b958b40fcd85430b7e9
Source dataset
uspto-grants-2012_07
Patent number
US08217063B2

Reaction notes

Loading…