Trifluoromethanesulfonic anhydride → HCID 10904469, compound

HRID 2306188Notes

Reaction equation

HRID 2306188 reaction equation
[Si:1]([O:8][CH2:9][C:10]1[N:11]=[CH:12][N:13](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:14]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[C:34]([C:36]1[CH:41]=[CH:40][C:39]([CH:42](O)[CH3:43])=[CH:38][C:37]=1[F:45])#[N:35].C(N(CC)C(C)C)(C)C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O>C(Cl)Cl.CO>[Si:1]([O:8][CH2:9][C:10]1[N:11]([CH:42]([C:39]2[CH:40]=[CH:41][C:36]([C:34]#[N:35])=[C:37]([F:45])[CH:38]=2)[CH3:43])[CH:12]=[N:13][CH:14]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 618241HCID 618241, compoundHCID 110842312-Fluoro-4-(1-hydroxyethyl)benzonitrile

Product 1

HCID 10904469HCID 10904469, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

A mixture of 4-(tert-butyldimethylsilyloxymethyl)-1-(triphenylmethyl)imidazole, as described above in Step D, (485 mg, 1.07 mmol), 1-(4-cyano-3-fluorophenyl)ethanol, as described above in Step C, (160 mg, 0.969 mmol), and N,N-diisopropylethylamine (0.219 mL, 1.26 mmol) in CH2Cl2 (12 mL) was cooled to −78° C., under argon. Trifluoromethanesulfonic anhydride (0.196 mL, 1.17 mmol) was added dropwise, and the mixture was stirred for 18 hours while it slowly warmed to ambient temperature. Methanol (15 mL) was added and the CH2Cl2 was distilled off in vacuo. The resulting methanolic solution was heated to reflux for 3 hours, then concentrated in vacuo to give a residue which was partitioned between saturated aqueous Na2CO3 (10 mL) and CH2Cl2 (20 mL). The aqueous layer was extracted further with CH2Cl2 (20 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography, eluting with a gradient of CH2Cl2—0% to 5% MeOH, to yield the titled product as a pale foam.

Workup

  1. temperatureslowly warmed to ambient temperature
  2. distillationthe CH2Cl2 was distilled off in vacuo
  3. temperatureThe resulting methanolic solution was heated
  4. temperatureto reflux for 3 hours
  5. concentrationconcentrated in vacuo
  6. customto give a residue which
  7. customwas partitioned between saturated aqueous Na2CO3 (10 mL) and CH2Cl2 (20 mL)
  8. extractionThe aqueous layer was extracted further with CH2Cl2 (20 mL)
  9. dry with materialThe combined organic extracts were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by silica gel chromatography
  13. washeluting with a gradient of CH2Cl2—0% to 5% MeOH

Sources & evidence

ORD record
ord-32d20c8a81fd4ca9aa2376f52694b513
Source dataset
uspto-grants-2002_08
Patent number
US06441017B1

Reaction notes

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