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

HRID 716417Notes

Reaction equation

HRID 716417 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-6c79b4091c654b5e862e2ad9f338f21a
Source dataset
uspto-grants-2015_11
Patent number
US09187522B2

Reaction notes

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