Water → Ethyl 3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropanoate

HRID 1760932Notes

Reaction equation

HRID 1760932 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]([CH2:11][CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([CH2:20][CH:21]([OH:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:16][CH:15]=2)[CH2:3][CH2:2]1.[H-].[Na+].[CH2:30](Br)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.O>CN(C)C=O>[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[N:4]([CH2:11][CH2:12][O:13][C:14]2[CH:15]=[CH:16][C:17]([CH2:20][CH:21]([O:27][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:18][CH:19]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 9929345Ethyl 3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoate

Product 1

HCID 9955952Ethyl 3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-benzyloxypropanoateYield 48.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of ethyl 3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4-yl)ethoxy]phenyl]-2-hydroxypropanoate (0.5 g, 1.34 mmol) obtained in example 13 in dry dimethyl formamide (5 mL) was added to a stirred ice cooled suspension of sodium hydride (60% dispension in oil) (0.08 g, 1.66 mmol) in dry dimethyl formamide (3 mL) under nitrogen atmosphere. The reaction mixture was stirred at 0° C. for 30 minutes followed by the addition of benzyl bromide (0.46 g, 2.69 mmol). The mixture was allowed to warm to 25° C. and stirring was continued for further 18 h. Water (25 mL) was added and extracted with ethyl acetate (2×50 mL). The combined organic layer was washed with water (50 mL), brine (50 mL) and dried Na2SO4 and filtered. The solvent was evaporated under reduced pressure and the residue was chromatographed over silica gel using a mixture of ethyl acetate and pet. ether (2:8) as eluent to afford the title compound (0.3 g) along with benzyl 3-[4-[2-(2,3-dihydro-1,4-benzoxazin-4yl)ethoxy]phenyl]-2-benzyloxypropanoate. This mixture (1:1) is used in example 47 without any separation.

Workup

  1. temperaturecooled
  2. temperatureto warm to 25° C.
  3. stirringstirring
  4. waitwas continued for further 18 h
  5. extractionextracted with ethyl acetate (2×50 mL)
  6. washThe combined organic layer was washed with water (50 mL), brine (50 mL) and dried Na2SO4
  7. filtrationfiltered
  8. customThe solvent was evaporated under reduced pressure
  9. customthe residue was chromatographed over silica gel using
  10. additiona mixture of ethyl acetate and pet. ether (2:8) as eluent

Sources & evidence

ORD record
ord-1e82dd46fad84e70a95407e68be6cc28
Source dataset
uspto-grants-2005_01
Patent number
US06846824B2

Reaction notes

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