Tetrahydrofuran → Tert-butyl 4-(4-amino-3-fluorobenzyl)piperidine-1-carboxylate

HRID 515289Notes

Reaction equation

HRID 515289 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[N+:22]([O-])=O)[CH:5]=[C:6]1[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.O1CCCC1.[F-].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)C>[NH2:22][C:21]1[CH:20]=[CH:19][C:4]([CH2:5][CH:6]2[CH2:7][CH2:8][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:16])[CH3:17])=[O:13])[CH2:10][CH2:11]2)=[CH:3][C:2]=1[F:1]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 522689Potassium FluorideHCID 67192635tert-Butyl 4-(3-fluoro-4-nitrobenzylidene)piperidine-1-carboxylate

Product 1

HCID 67193052Tert-butyl 4-(4-amino-3-fluorobenzyl)piperidine-1-carboxylateYield 100.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 3283Diethyl EtherSolvent

Procedure

A flask was charged with palladium (II)acetate (1.486 mmol, 0.334 g), tert-butyl 4-(3-fluoro-4-nitrobenzylidene)piperidine-1-carboxylate (29.7 mmol, 10 g) and tetrahydrofuran (15 mL) and sealed and purged with nitrogen. A solution of potassium fluoride (59.5 mmol, 3.45 g, in 50 ml water) was added via a syringe. Polymethylhydrosiloxane (119 mmol, 7.13 mL) was added dropwise (caution, gas evolution) and the reaction stirred at room temperature for 1 hour. Diethyl ether (10 mL) was added to the reaction mixture. After 5 minutes of stirring the reaction mixture was filtered through celite and diluted with water and ethyl acetate. The organic layer was washed with water and brine, dried over magnesium sulfate and concentrated under vacuum. The residue was purified by silica column chromatography (eluent: 20%-50% ethyl acetate in heptane) to give the intermediate tert-butyl 4-(4-amino-3-fluorobenzyl)piperidine-1-carboxylate (9.23 g).

Workup

  1. customsealed
  2. custompurged with nitrogen
  3. stirringAfter 5 minutes of stirring the reaction mixture
  4. filtrationwas filtered through celite
  5. additiondiluted with water and ethyl acetate
  6. washThe organic layer was washed with water and brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified by silica column chromatography (eluent: 20%-50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-3daeda45b92945c0bbfe1b71e6b3160e
Source dataset
uspto-grants-2015_08
Patent number
US09108939B2

Reaction notes

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