Water → HCID 9886735, compound

HRID 1937741Notes

Reaction equation

HRID 1937741 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7]2[O:12][C:11]([CH3:14])([CH3:13])[C@H:10]([OH:15])[C@@H:9]([NH:16][C:17](=[O:26])[C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=3)[C:8]=2[CH:27]=1)(=[O:3])[CH3:2].O.FC(F)(F)C(O)=[O:32].FC(F)(F)C(OI(C1C=CC=CC=1)OC(=O)C(F)(F)F)=O>C(#N)C>[F:24][C:22]1[CH:23]=[C:18]([CH:19]=[C:20]([F:25])[CH:21]=1)[C:17]([NH:16][C@H:9]1[C:8]2[CH:27]=[C:4]([C:1](=[O:3])[CH2:2][OH:32])[CH:5]=[CH:6][C:7]=2[O:12][C:11]([CH3:14])([CH3:13])[C@@H:10]1[OH:15])=[O:26]

Participants

6

Reactant 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 102317Bis(trifluoroacetoxy)iodobenzeneHCID 170378Tidembersat

Product 1

HCID 9886735HCID 9886735, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(3R,4S)-6-Acetyl-4-(3,5-difluorobenzamido)-3,4-dihydro-2,2-dimethyl-3-hydroxy-2H-1-benzopyran D3 (1.88 g, 5.0 mmol) (Example 4 of WO95/34545) was dissolved in acetonitrile (25ml), water (5 ml) and trifluoroacetic acid (0.77 ml, 10.0 mmol). [Bis(trifluoroacetoxy)iodo]benzene (4.30 g, 10.0 mmol) was added and the reaction stirred under reflux for three hours. The reaction mixture was allowed to cool and the acetonitrile was removed in vacuo, the resulting material being partitioned between water (50 ml) and dichloromethane (125 ml). The aqueous layer was extracted with further portions of dichloromethane (3×25 ml) and the combined organic extracts were dried over magnesium sulphate, filtered and the solvent removed in vacuo. The resulting yellow solid was purified by column chromatography on silica, eluting with 20% to 40% ethyl acetate in hexane to afford the title compound as a white solid (0.70 g, 36%, m.p. 179.4° C.).

Workup

  1. temperatureunder reflux for three hours
  2. temperatureto cool
  3. customthe acetonitrile was removed in vacuo
  4. customthe resulting material being partitioned between water (50 ml) and dichloromethane (125 ml)
  5. extractionThe aqueous layer was extracted with further portions of dichloromethane (3×25 ml)
  6. dry with materialthe combined organic extracts were dried over magnesium sulphate
  7. filtrationfiltered
  8. customthe solvent removed in vacuo
  9. customThe resulting yellow solid was purified by column chromatography on silica
  10. washeluting with 20% to 40% ethyl acetate in hexane

Sources & evidence

ORD record
ord-735a55d5d83d4290a4e1b986af91af95
Source dataset
uspto-grants-2002_05
Patent number
US06395909B1

Reaction notes

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