Benzene, 1-bromo-3-iodo- → Tert-butyl 3-(3-bromophenyl)-3-hydroxypiperidine-1-carboxylate

HRID 1505920Notes

Reaction equation

HRID 1505920 reaction equation
C([Li])CCC.[Br:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9](I)[CH:8]=1.[C:14]([N:21]1[CH2:26][CH2:25][CH2:24][C:23](=[O:27])[CH2:22]1)([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15]>C1COCC1>[C:17]([O:16][C:14]([N:21]1[CH2:26][CH2:25][CH2:24][C:23]([C:9]2[CH:10]=[CH:11][CH:12]=[C:7]([Br:6])[CH:8]=2)([OH:27])[CH2:22]1)=[O:15])([CH3:20])([CH3:18])[CH3:19]

Participants

5

Reactant 3

HCID 11561Benzene, 1-bromo-3-iodo-HCID 2756825Tert-butyl 3-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 58266359Tert-butyl 3-(3-bromophenyl)-3-hydroxypiperidine-1-carboxylateYield 33%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

n-Butyllithium (2.5 M in hexanes, 7.6 mL, 19.0 mmol) was added over 10 min to a solution of 1-bromo-3-iodobenzene (5.37 g, 19.0 mmol) in THF (100 mL) at −78° C. After 15 min, a solution of 1-boc-3-piperidone (3.44 g, 17.3 mmol) in THF (10 mL) was added and the resultant reaction mixture was left to stir at −78° C. for 1 h, then warmed to 0° C. and quenched by the addition of saturated aqueous ammonium chloride (50 mL). The mixture was allowed to warm to ambient temperature and partitioned between ethyl acetate (400 mL) and water (150 mL). The organic layer was separated, dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo. The resultant residue was purified by flash chromatography (silica, 80 g column, ISCO, 0-100% ethyl acetate in cyclohexane) to afford the title compound as a colourless gum (1.99 g, 33%). 1H NMR (CDCl3, 300 MHz): 7.70-7.67 (m, 1H); 7.46-7.40 (m, 2H); 7.24-7.20 (m, 1H); 4.15-3.88 (m, 2H); 3.21-3.08 (m, 1H); 2.93-239 (m, 1H); 2.03-1.82 (m, 2H); 1.75-1.51 (m, 2H); 1.48 (s, 9H). LCMS (Method B): RT=3.88 min, M-[Boc-18]+238.

Workup

  1. customthe resultant reaction mixture
  2. waitwas left
  3. temperaturewarmed to 0° C.
  4. customquenched by the addition of saturated aqueous ammonium chloride (50 mL)
  5. temperatureto warm to ambient temperature
  6. custompartitioned between ethyl acetate (400 mL) and water (150 mL)
  7. customThe organic layer was separated
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe resultant residue was purified by flash chromatography (silica, 80 g column, ISCO, 0-100% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-4d25c9497aef4096ac3d2fdfc60e3708
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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