Dichloromethane → 1-benzhydryl-3-fluoroazetidine

HRID 1292736Notes

Reaction equation

HRID 1292736 reaction equation
[CH:1]([N:14]1[CH2:17][CH:16](O)[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.ClCCl.COCCN(S(F)(F)[F:32])CCOC.C(=O)(O)[O-].[Na+]>O>[CH:1]([N:14]1[CH2:17][CH:16]([F:32])[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

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 3304481-(Diphenylmethyl)azetidin-3-olHCID 516892Sodium BicarbonateHCID 2734690(Bis(2-methoxyethyl)amino)sulfur trifluoride

Product 1

HCID 73305071-benzhydryl-3-fluoroazetidine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 250 mL, round bottom flask was charged with 3.0 g (12.5 mmol) of 1-benzhydryl-3-hydroxyazetidine and 80 mL of dichloromethane. To the stirring solution at −78° C. was added 4.6 mL (25 mmol) of [bis(2-methoxyethyl)amino]sulfur trifluoride via addition funnel over a period of about 3 h. The reaction mixture was allowed to warm slowly to ambient temperature overnight. The reaction mixture was added portionwise (with caution) to a large extractor containing water and saturated aqueous sodium bicarbonate solution. The mixture was extracted three times with 80 mL of dichloromethane. The combined organic layers were washed sequentially with saturated aqueous sodium bicarbonate solution, water and saturated aqueous brine, dried over sodium sulfate, and concentrated in vacuo. Purification by flash chromatography using a Biotage® system (gradient, hexane to 80% ethyl acetate/hexane) afforded the desired product. LC/MS 242.1 (M+1).

Workup

  1. additionvia addition funnel over a period of about 3 h
  2. additionThe reaction mixture was added portionwise (with caution) to a large extractor
  3. extractionThe mixture was extracted three times with 80 mL of dichloromethane
  4. washThe combined organic layers were washed sequentially with saturated aqueous sodium bicarbonate solution, water and saturated aqueous brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification by flash chromatography

Sources & evidence

ORD record
ord-eead71c4ac2d47849e6a2237e198bcb3
Source dataset
uspto-grants-2007_07
Patent number
US07238683B2

Reaction notes

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