Tetrahydrofuran → Trifluoroacetic acid

HRID 2111529Notes

Reaction equation

HRID 2111529 reaction equation
[CH:1]([N:14]1[CH2:17][C:16](=[O:18])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:19][C:20]([Si](C)(C)C)([F:22])[F:21].[F-].[Cs+].C1[CH2:33][O:32]CC1>>[CH:1]([N:14]1[CH2:17][C:16]([C:20]([F:22])([F:21])[F:19])([OH:18])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1.[C:33]([OH:32])([C:20]([F:22])([F:21])[F:19])=[O:18]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 25953Cesium fluorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 37355581-(Diphenylmethyl)azetidin-3-one

Product 2

HCID 6422Trifluoroacetic acidHCID 576391211-(Diphenylmethyl)-3-(trifluoromethyl)azetidin-3-ol

Procedure

To a solution of 1-benzhydryl-azetidin-3-one (400 mg, 1.69 mmol) in THF (5 mL), trifluoromethyltrimethylsilane (360 mg, 2.53 mmol) and cesium fluoride(390 mg, 2.57 mmol) were added. The reaction mixture was stirred at rt. for 1 hr. Then it was quenched with 5 mL saturated NH4Cl solution and tetrabutylammonium fluoride (200 mg) was added. The resulting reaction mixture was stirred at rt. for three days. It was then extracted with ether (3×20 mL). The organic layers were combined, dried (MgSO4) and concentrated to give an orange oil as crude product. It was then purified by Prep.HPLC column to afford a white solid as final product as TFA salt. (350 mg, 49% yield). Retention time: 1.442 min. 1H NMR (500 MHz, MeOD) δ ppm 3.92 (d, J=11.29 Hz, 2 H) 4.35 (d, J=11.60 Hz, 2 H) 5.44 (s, 1 H) 7.34-7.55 (m, 10 H).

Workup

  1. customThen it was quenched with 5 mL saturated NH4Cl solution and tetrabutylammonium fluoride (200 mg)
  2. additionwas added
  3. customThe resulting reaction mixture
  4. stirringwas stirred at rt
  5. waitfor three days
  6. extractionIt was then extracted with ether (3×20 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customto give an orange oil as crude product
  10. customIt was then purified by Prep.HPLC column

Sources & evidence

ORD record
ord-95f23482c76e47a4a6fa5bdd54386fba
Source dataset
uspto-grants-2009_04
Patent number
US07521442B2

Reaction notes

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