p-Fluoronitrobenzene → Tert-butyl 4-(4-nitrophenoxy)piperidine-1-carboxylate

HRID 1988360Notes

Reaction equation

HRID 1988360 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].OC1CCNCC1.C([O-])(C)(C)C.[K+].F[C:29]1[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][CH:30]=1>C1COCC1>[N+:35]([C:32]1[CH:33]=[CH:34][C:29]([O:14][CH:11]2[CH2:12][CH2:13][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:9][CH2:10]2)=[CH:30][CH:31]=1)([O-:37])=[O:36]

Participants

6

Reactant 4

HCID 9590p-FluoronitrobenzeneHCID 79341Piperidin-4-olHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 2794776Tert-butyl 4-(4-nitrophenoxy)piperidine-1-carboxylateYield 47%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
23 °C

Procedure

A solution of 2.01 g (10 mmol) of N-Boc-4-hydroxypiperidine (prepared in a standard fashion starting, from commercial 4-hydroxypiperidine) in 10 ml of dry THF is added dropwise to a solution of 1.23 g (11 mmol) of tBuO−K+ in 10 ml of dry THF in a three necked flask, under an inert atmosphere, cooled by an ice bath. After agitation for 30 minutes at 0° C., a solution of 1.06 ml (10 mmol) of 4-fluoronitrobenzene in 10 ml of dry THF is added dropwise. The reaction mixture is agitated for 5 hours at 23° C. and finally poured into 25 ml of a water+ice mixture. The product is extracted using 50 ml of ethyl acetate. After decantation, the organic phase is washed twice with 25 ml of water and 25 ml of salt water. The organic solution is dried over magnesium sulphate, followed by filtration and concentration of the filtrate under vacuum to produce a residue which is purified on a silica column (eluant:heptane/ethyl acetate: 8/2). The pure fractions are collected and evaporated under vacuum. The expected product is obtained in the form of a pale yellow powder with a yield of 47%. Melting point: 97-98° C.

Workup

  1. temperaturecooled by an ice bath
  2. extractionThe product is extracted
  3. washAfter decantation, the organic phase is washed twice with 25 ml of water and 25 ml of salt water
  4. dry with materialThe organic solution is dried over magnesium sulphate
  5. filtrationfollowed by filtration and concentration of the filtrate under vacuum
  6. customto produce a residue which
  7. customis purified on a silica column (eluant:heptane/ethyl acetate: 8/2)
  8. customThe pure fractions are collected
  9. customevaporated under vacuum

Sources & evidence

ORD record
ord-8c7394b2a3c44eb289c2227647e295a9
Source dataset
uspto-grants-2009_06
Patent number
US07553976B2

Reaction notes

Loading…