(Diethylamino)sulfur trifluoride → Tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-fluoropiperidine-1-carboxylate

HRID 912531Notes

Reaction equation

HRID 912531 reaction equation
[CH2:1]([O:3][C:4](=[O:20])[CH2:5][C:6]1(O)[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)[CH3:2].C(N(S(F)(F)[F:27])CC)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:20])[CH2:5][C:6]1([F:27])[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)[CH3:2]

Participants

5

Reactant 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 10469302Tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-hydroxypiperidine-1-carboxylate

Product 1

HCID 59410709Tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-fluoropiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-hydroxypiperidine-1-carboxylate (12 g) in DCM (60 ml) at −78° C. under nitrogen was added by syringe diethylaminosulfur trifluoride (DAST) (8.3 ml). The mixture was stirred at −78° C. for 3 hours, then slowly warming up to rt, the mixture was then poured to aqueous sodium bicarbonate (200 ml), extracted with ethyl acetate (200 ml+100 ml), organic layer dried over sodium sulphate, solvent removed under vacuum. The oily residue was taken into ethanol (150 ml) and water (150 ml). Magnesium sulphate (5.4 g) was then added, followed by potassium permanganate (7.2 g). The mixture was stirred at rt for 1 hour, then extracted with ethyl acetate (600 ml). Organic layer was washed with brine (150 ml), dried over sodium sulphate, solvent removed under vacuum, residue was columned on silica gel using heptane:EtOAc (7:1) as eluant to give tert-butyl 4-(2-ethoxy-2-oxoethyl)-4-fluoropiperidine-1-carboxylate (3.8 g) as a colourless oil. 1H NMR (CDCl3) δ: 4.16 (q, 2H), 3.95 (br, 2H), 3.10 (t, br, 2H), 2.64 (d, 2H), 1.93 (t, br, 2H), 1.6-1.85 (m, 2H), 1.46 (s, 9H), 1.27 (t, 3H).

Workup

  1. temperatureslowly warming up to rt
  2. extractionextracted with ethyl acetate (200 ml+100 ml), organic layer
  3. dry with materialdried over sodium sulphate, solvent
  4. customremoved under vacuum
  5. additionMagnesium sulphate (5.4 g) was then added
  6. stirringThe mixture was stirred at rt for 1 hour
  7. extractionextracted with ethyl acetate (600 ml)
  8. washOrganic layer was washed with brine (150 ml)
  9. dry with materialdried over sodium sulphate, solvent
  10. customremoved under vacuum, residue

Sources & evidence

ORD record
ord-0990be6a1056447281087ba309b9d54f
Source dataset
uspto-grants-2011_09
Patent number
US08026236B2

Reaction notes

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