1-(4-Bromophenoxy)heptane → Tert-butyl 4-(4-(heptyloxy)phenyl)-4-hydroxypiperidine-1-carboxylate

HRID 1623015Notes

Reaction equation

HRID 1623015 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])=[CH:4][CH:3]=1.C([Li])CCC.[O:21]=[C:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1>C1COCC1>[CH2:9]([O:8][C:5]1[CH:6]=[CH:7][C:2]([C:22]2([OH:21])[CH2:23][CH2:24][N:25]([C:28]([O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[O:29])[CH2:26][CH2:27]2)=[CH:3][CH:4]=1)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]

Participants

5

Reactant 3

HCID 5991021-(4-Bromophenoxy)heptaneHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 86689685Tert-butyl 4-(4-(heptyloxy)phenyl)-4-hydroxypiperidine-1-carboxylateYield 41.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirring solution of 1-bromo-4-(heptyloxy)benzene (668 mg, 2.46 mmol) in THF (5 mL) at −78° C. was added butyllithium (985 μl, 2.46 mmol). After 30 min, a solution of tert-butyl 4-oxopiperidine-1-carboxylate (491 mg, 2.46 mmol) in THF (2 mL) was added. After 10 min, the cooling bath was removed and the reaction mixture stirred for 16 h. The reaction mixture was poured onto NH4Cl (50 mL) and extracted with Et2O (3×20 mL). The combined organics were washed with water (20 mL), dried over MgSO4 and evaporated. The crude product was purified by column chromatography (5-70% AcMe in iso-hexanes) to afford 0.4 g (33%) of tert-butyl 4-(4-(heptyloxy)phenyl)-4-hydroxypiperidine-1-carboxylate. LCMS-ESI (m/z) calculated for C23H37NO4: 391.5; found 414.0 [M+Na]+, tR=2.24 min. (Method 4).

Workup

  1. waitAfter 10 min
  2. customthe cooling bath was removed
  3. additionThe reaction mixture was poured onto NH4Cl (50 mL)
  4. extractionextracted with Et2O (3×20 mL)
  5. washThe combined organics were washed with water (20 mL)
  6. dry with materialdried over MgSO4
  7. customevaporated
  8. customThe crude product was purified by column chromatography (5-70% AcMe in iso-hexanes)

Sources & evidence

ORD record
ord-934126214d4c4ab19c21050f7c980beb
Source dataset
uspto-grants-2014_07
Patent number
US08778923B2

Reaction notes

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