Tetrabutylammonium Fluoride → 1-Azetidinecarboxylic acid, 3-(fluoromethyl)-, 1,1-dimethylethyl ester

HRID 717499Notes

Reaction equation

HRID 717499 reaction equation
CS(O[CH2:6][CH:7]1[CH2:10][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:8]1)(=O)=O.[F-:18].C([N+](CCCC)(CCCC)CCCC)CCC>>[F:18][CH2:6][CH:7]1[CH2:10][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:8]1

Participants

3

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 21959416Tert-butyl 3-((methanesulfonyloxy)methyl)azetidine-1-carboxylate

Product 1

HCID 768501961-Azetidinecarboxylic acid, 3-(fluoromethyl)-, 1,1-dimethylethyl ester

Procedure

A mixture of tert-butyl 3-(((methylsulfonyl)oxy)methyl)azetidine-1-carboxylate (12.5 g, 47 mmol) and 235 mL tetrabutylammonium fluoride (1M solution in THF, 5 equiv.) was heated at reflux for 18 h. The reaction mixture was cooled to room temperature and excess THF was removed on a rotary evaporator. The residue was dissolved in ethyl acetate. The organic phase was washed with sat'd aqueous NaHCO3, washed with water, washed with brine, dried over Na2SO4, filtered and concentrated on a rotary evaporator to give the crude product. This crude product was purified by silica gel chromatography to afford tert-butyl 3-(fluoromethyl)azetidine-1-carboxylate as clear oil (7.5 g). 1H NMR (DMSO-d6): δ 4.52 (dd, 2H), 3.89 (br, 2H), 3.61 (br, 2H), 2.92-2.77 (m, 1H), 1.36 (s, 9H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 18 h
  3. customexcess THF was removed on a rotary evaporator
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washThe organic phase was washed with sat'd aqueous NaHCO3
  6. washwashed with water
  7. washwashed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated on a rotary evaporator
  11. customto give the crude product
  12. customThis crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-2b0d9e40de884ad49fbb93f8ed0b9240
Source dataset
uspto-grants-2015_11
Patent number
US09193714B2

Reaction notes

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