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

HRID 2396722Notes

Reaction equation

HRID 2396722 reaction equation
[NH2:1][C:2]1[C:6]2[CH:7]=[CH:8][C:9]([O:11][CH2:12][O:13][CH3:14])=[CH:10][C:5]=2[O:4][N:3]=1.[H-].[Na+].Cl[CH2:18][CH2:19][N:20]1[CH2:25][CH2:24][S:23][CH2:22][CH2:21]1.CO.C(Cl)Cl>CN(C)C=O.CCOC(C)=O>[CH3:14][O:13][CH2:12][O:11][C:9]1[CH:8]=[CH:7][C:6]2[C:2]([NH:1][CH2:18][CH2:19][N:20]3[CH2:25][CH2:24][S:23][CH2:22][CH2:21]3)=[N:3][O:4][C:5]=2[CH:10]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 96140Thiomorpholine, 4-(2-chloroethyl)-HCID 110087953-Amino-6-methoxymethoxy-1,2-benzisoxazoleHCID 21226129Dichloromethane methanol

Product 1

HCID 154351386-Methoxymethoxy-N-[2-(4-thiomorpholinyl)ethyl]-1,2-benzisoxazol-3-amineYield 30%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-amino-6-methoxymethoxy-1,2-benzisoxazole (4.0 g) in N,N-dimethylformamide (DMF) (50 ml) was added sodium hydride (0.74 g) under nitrogen. The reaction was stirred one hour at ambient temperature. A solution of 4-(2-chloroethyl)thiomorpholine (3.6 g) in DMF (25 ml) was added to the reaction and heated to 125° C. for three hours. TLC (5% MeOH/CH2Cl2) revealed the absence of starting material. The reaction was diluted with EtOAc (1 l), washed with brine (4×500 ml), dried (MgSO4), and concentrated in vacuo. Flash column chromatography (silica gel) eluting with 5% acetone/CH2Cl2 afforded the the product (2.0 g).

Workup

  1. temperatureheated to 125° C. for three hours
  2. washwashed with brine (4×500 ml)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. washFlash column chromatography (silica gel) eluting with 5% acetone/CH2Cl2

Sources & evidence

ORD record
ord-7291d2e58ca9477091b9a7ad3cafa807
Source dataset
uspto-grants-1996_02
Patent number
US05494908

Reaction notes

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