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

HRID 1292514Notes

Reaction equation

HRID 1292514 reaction equation
[NH2:1][C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][N:3]=1.[H-].[Na+].Cl[CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.CO.C(Cl)Cl>CN(C)C=O>[N:16]1([CH2:15][CH2:14][NH:1][C:2]2[C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=3[O:4][N:3]=2)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 767274-(2-Chloroethyl)morpholineHCID 27797491,2-Benzoxazol-3-amineHCID 21226129Dichloromethane methanol

Product 1

HCID 15453430N-[2-(4-Morpholinyl)ethyl]-1,2-benzisoxazol-3-amineYield 38.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 3-amino-1,2-benzisoxazole (3.5 g) in N,N-dimethylformamide (DMF) (100 ml) was added sodium hydride (0.8 g) under nitrogen. The reaction was stirred one hour at ambient temperature. A solution of 4-(2-chloroethyl)morpholine (4.0 g) in DMF (50 ml) was added followed by heating to 120° C. for one hour. TLC (5% MeOH/DCM) analysis revealed the absence of starting material. The reaction was quenched with water and extracted with EtOAc. The organic layer was washed with water, dried (MgSO4), and concentrated in vacuo. Flash column chromatography (silica gel) eluting with 1.5-2.5% MeOH/DCM afforded the product (2.5 g), m.p. 79°-80° C.

Workup

  1. temperatureby heating to 120° C. for one hour
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc
  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 1.5-2.5% MeOH/DCM

Sources & evidence

ORD record
ord-d90baf76c04d46aaa7fb0283540ab191
Source dataset
uspto-grants-1998_05
Patent number
US05756754

Reaction notes

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