Dimethylformamide → HCID 58720299, compound

HRID 1787528Notes

Reaction equation

HRID 1787528 reaction equation
[CH3:1][C:2]([CH3:5])([O-:4])[CH3:3].[K+].[O:7]1[C:11]2[CH:12]=[CH:13][S:14][C:10]=2[C:9]([C:15]2[CH:16]=[C:17]([OH:21])[CH:18]=[CH:19][CH:20]=2)=[N:8]1.CN(C)C=[O:25]>>[CH3:1][C@@:2]([OH:4])([CH2:5][O:21][C:17]1[CH:18]=[CH:19][CH:20]=[C:15]([C:9]2[C:10]3[S:14][CH:13]=[CH:12][C:11]=3[O:7][N:8]=2)[CH:16]=1)[CH2:3][OH:25]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 140972423-Thieno[2,3-d]isoxazol-3-yl-phenolHCID 23665647Potassium tert-butoxide

Product 1

HCID 58720299HCID 58720299, compoundYield 53%

Conditions

Temperature
50 °C

Procedure

Add potassium t-butoxide (14.2 g, 0.126 mol) in small portions under nitrogen to a stirred solution of 3-thieno[2,3-d]isoxazol-3-yl-phenol (example 1, 27.5 g, 0.126 mol) and dimethylformamide (200 mL). After 10 min. add (2R)-(+)-2-methylglycidyl-4-nitrobenzoate (10.0 g, 0.0.0422 mol, Aldrich Chemical Company) and rinse through with dimethylformamide (50 mL). Heat to 50° C. and stir for two hours. Pour into ice water (1200 mL) and extract with ethyl acetate (add ammonium chloride to aid separation). Separate the organic phase, dry (Na2SO4), filter and concentrate in vacuo. Purify the residue by flash chromatography over silica gel, elute with 4-7% methanol in dichloromethane and concentrate the desired fractions. Purify again by preparative chromatography (silica gel, elute with 3-5% methanol in dichloromethane) to give a tan solid (6.8 g, 53% yield).

Workup

  1. washrinse through with dimethylformamide (50 mL)
  2. additionPour into ice water (1200 mL)
  3. extractionextract with ethyl acetate (add ammonium chloride to aid separation)
  4. customSeparate the organic phase
  5. dry with materialdry (Na2SO4)
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customPurify the residue by flash chromatography over silica gel
  9. washelute with 4-7% methanol in dichloromethane
  10. concentrationconcentrate the desired fractions
  11. customPurify again by preparative chromatography (silica gel, elute with 3-5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-ea76e06c2f7f479ea8d4e7cb865537ab
Source dataset
uspto-grants-2009_03
Patent number
US07511046B2

Reaction notes

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