Sodium hydride → 6-Methoxy-N-[2-(4-morpholinyl)ethyl]-1,2-benzisoxazol-3-amine

HRID 582867Notes

Reaction equation

HRID 582867 reaction equation
[NH2:1][C:2]1[C:6]2[CH:7]=[CH:8][C:9]([O:11][CH3:12])=[CH:10][C:5]=2[O:4][N:3]=1.[H-].[Na+].Cl[CH2:16][CH2:17][N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.CO.C(Cl)Cl>CN(C)C=O>[CH3:12][O:11][C:9]1[CH:8]=[CH:7][C:6]2[C:2]([NH:1][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[N:3][O:4][C:5]=2[CH:10]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 767274-(2-Chloroethyl)morpholineHCID 106785796-Methoxy-1,2-benzoxazol-3-amineHCID 21226129Dichloromethane methanol

Product 1

HCID 187964566-Methoxy-N-[2-(4-morpholinyl)ethyl]-1,2-benzisoxazol-3-amineYield 48.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 3-amino-6-methoxy-1,2-benzisoxazole (5.5 g) in N,N-dimethylformamide (DMF) (100 ml) was added sodium hydride (1.2 g) under nitrogen. The reaction was stirred one hour at ambient temperature. A solution of 4-(2-chloroethyl)morpholine (5.4 g) in DMF (50 ml) was added to the reaction and heated to 125° C. for one hour. TLC (5% MeOH/DCM) revealed the absence of starting material. The reaction was quenched with water (1 l) and extracted with EtOAc (2 l). The organic layer was washed with water, dried (MgSO4), and concentrated in vacuo. Flash column chromatography (silica gel) eluting with 3-4% MeOH/DCM afforded the product (4.5 g), m.p. 85-86° C.

Workup

  1. temperatureheated to 125° C. for one hour
  2. customThe reaction was quenched with water (1 l)
  3. extractionextracted with EtOAc (2 l)
  4. washThe organic layer was washed with water
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. washFlash column chromatography (silica gel) eluting with 3-4% MeOH/DCM

Sources & evidence

ORD record
ord-81773230ad804df4be9bfbb52eb01c3b
Source dataset
uspto-grants-1999_07
Patent number
US05925766

Reaction notes

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