Acetohydroxamic Acid → 3-Amino-6-methoxymethoxy-1,2-benzisoxazole

HRID 582872Notes

Reaction equation

HRID 582872 reaction equation
C([NH:4][OH:5])(=O)C.CC(C)([O-])C.[K+].F[C:13]1[CH:20]=[C:19]([O:21][CH2:22][O:23][CH3:24])[CH:18]=[CH:17][C:14]=1[C:15]#[N:16]>CN(C)C=O.CC(C)=O.C(Cl)(Cl)Cl.CCOC(C)=O>[NH2:16][C:15]1[C:14]2[CH:17]=[CH:18][C:19]([O:21][CH2:22][O:23][CH3:24])=[CH:20][C:13]=2[O:5][N:4]=1

Participants

7

Reactant 3

HCID 1990Acetohydroxamic Acid2×HCID 109541382-Fluoro-4-(methoxymethoxy)-benzonitrileHCID 23665647Potassium tert-butoxide

Product 1

HCID 110087953-Amino-6-methoxymethoxy-1,2-benzisoxazoleYield 125.9%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolventHCID 15930782Chloroform acetoneSolvent

Procedure

To a stirred solution of acetohydroxamic acid (3.88 g) in N,N-dimethylformamide (DMF) (120 ml) was added potassium tertiarybutoxide (tBuOK) (5.80 g) under N2. After one hour of stirring 2-fluoro-4-(methoxymethoxy)-benzonitrile (6.0 g) was added. Stirring continued for 16 hours. TLC (silica gel) in 10% acetone/CHCl3 showed the presence of starting material. An additional 1 equivalent of acetohydroxamic acid and tBuOk were added in DMF (120 ml). After one hour the reaction was diluted with EtOAc (2 l), filtered, washed filtrate with brine (4×11), dried (MgSO4), and concentrated in vacuo. Flash column chromatography (silica gel) was performed eluting with 2.5% acetone/CH2Cl2 solution affording 8.1 g of the product, m.p. 88-89° C.

Workup

  1. filtrationfiltered
  2. washwashed filtrate with brine (4×11)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. washFlash column chromatography (silica gel) was performed eluting with 2.5% acetone/CH2Cl2 solution

Sources & evidence

ORD record
ord-da4ed3fa860c43d981900e496e2393b9
Source dataset
uspto-grants-1999_07
Patent number
US05925766

Reaction notes

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