Tetrabutylammonium Fluoride → (S)-1-Boc-2-(fluoromethyl)azetidine

HRID 10393Notes

Reaction equation

HRID 10393 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12]OS(C)(=O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F-:18].C([N+](CCCC)(CCCC)CCCC)CCC>>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][F:18])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

3

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 59371380tert-Butyl (S)-2-(((methylsulfonyl)oxy)methyl)azetidine-1-carboxylate

Product 1

HCID 66701900(S)-1-Boc-2-(fluoromethyl)azetidine

Procedure

2-(S)-Methanesulfonyloxymethyl-azetidine-1-carboxylic acid tert-butyl ester (5.62 g, 21.2 mmol) was treated with tetrabutylammonium fluoride (1 M solution in THF, 191 mL) under N2, heated to reflux for 1 hour, cooled to ambient temperature, concentrated to 50 mL, treated with water (100 mL) and extracted with ethyl acetate (2×250 mL). The combined ethyl acetate layers were washed with 0.25 M HCl (100 mL), washed with NaHCO3 solution, washed with brine, dried (MgSO4), filtered, concentrated and chromatographed (10:1 and then 5:1 hexane:ethyl acetate) to provide 2.9 g (72%). 1H NMR (300 MHz, CDCl3) δ 1.44 (s, 9 H) 2.26 (m, 2 H) 3.84 (t, J=7.46 Hz, 2 H) 4.35 (m, 1 H) 4.42 (ddd, J=46.36, 9.92, 2.71 Hz, 1 H) 4.72 (ddd, J=48.31, 10.00, 3.05 Hz, 1 H).

Workup

  1. temperatureheated
  2. temperatureto reflux for 1 hour
  3. concentrationconcentrated to 50 mL
  4. additiontreated with water (100 mL)
  5. extractionextracted with ethyl acetate (2×250 mL)
  6. washThe combined ethyl acetate layers were washed with 0.25 M HCl (100 mL)
  7. washwashed with NaHCO3 solution
  8. washwashed with brine
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customchromatographed (10:1
  13. custom5:1 hexane:ethyl acetate) to provide 2.9 g (72%)

Sources & evidence

ORD record
ord-d77490cfe1ed472b8c43e116c87aa2d2
Source dataset
uspto-grants-2006_08
Patent number
US07094790B2

Reaction notes

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