Tert-butyl 2-(3-hydroxypropyl)piperidine-1-carboxylate → 3-(5-Bromo-2-fluorobenzyloxy)-1-[1-(t-butoxycarbonyl)piperidin-2-yl]propane

HRID 1066813Notes

Reaction equation

HRID 1066813 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[CH2:14][CH2:15][CH2:16][OH:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].[Br:24][C:25]1[CH:26]=[CH:27][C:28]([F:33])=[C:29]([CH:32]=1)[CH2:30]Br>O1CCCC1.C(Cl)Cl>[Br:24][C:25]1[CH:26]=[CH:27][C:28]([F:33])=[C:29]([CH:32]=1)[CH2:30][O:17][CH2:16][CH2:15][CH2:14][CH:9]1[CH2:10][CH2:11][CH2:12][CH2:13][N:8]1[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7]

Participants

6

Reactant 3

HCID 10900840Tert-butyl 2-(3-hydroxypropyl)piperidine-1-carboxylateHCID 135532954-Bromo-2-(bromomethyl)-1-fluorobenzeneHCID 23665647Potassium tert-butoxide

Product 1

HCID 211960863-(5-Bromo-2-fluorobenzyloxy)-1-[1-(t-butoxycarbonyl)piperidin-2-yl]propaneYield 50%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

3-[1-(t-Butoxycarbonyl)piperidin-2-yl]propanol (800 mg, 3.29 mmol) was taken up in tetrahydrofuran (17 ml), cooled to −40° C., and treated with potassium t-butoxide (1 M in tetrahydrofuran, 3.62 ml, 3.62 mmol). The resulting mixture was stirred at −40° C. for about 35 minutes, then cooled to −78° C. To this mixture was then added 5-bromo-2-fluorobenzyl bromide (881 mg, 3.29 mmol) as a solution in tetrahydrofuran (5 ml). The resultant yellow reaction mixture was slowly warmed to 0° C. and stirred for about four hours. The reaction mixture was diluted with methylene chloride and washed with 1 M potassium carbonate and brine. The organic fraction was dried over sodium sulfate, filtered, and concentrated in vacuo. The crude oil was purified by high performance liquid chromatography, yielding 707 mg (50%) of the title intermediate as a clear oil.

Workup

  1. temperaturecooled to −78° C
  2. temperatureThe resultant yellow reaction mixture was slowly warmed to 0° C.
  3. stirringstirred for about four hours
  4. washwashed with 1 M potassium carbonate and brine
  5. dry with materialThe organic fraction was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude oil was purified by high performance liquid chromatography

Sources & evidence

ORD record
ord-7614dc538d59408793cd7e31cecb893b
Source dataset
uspto-grants-2001_06
Patent number
US06245761B1

Reaction notes

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