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

HRID 1003329

Reaction equation

HRID 1003329 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-85ae87bbae874b66a59fb7ff92395934
Source dataset
uspto-grants-2000_04
Patent number
US06046203

Linked notes

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