tert-Butyl 4-formylpiperidine-1-carboxylate → HCID 66723571, compound

HRID 1476264Notes

Reaction equation

HRID 1476264 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1.[CH:20]([CH: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)=[O:21]>C1COCC1>[Cl:19][C:16]1[CH:17]=[CH:18][C:13]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[CH:20]([OH:21])[CH:22]2[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[O:29])[CH2:24][CH2:23]2)=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 1514430tert-Butyl 4-formylpiperidine-1-carboxylateHCID 129394052-Bromo-4'-chloro-1,1'-biphenyl2×HCID 178418339Butyllithium

Product 1

HCID 66723571HCID 66723571, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

n-Butyl lithium (29.4 mL, 47.09 mmol) was added dropwise to a solution of 2-bromo-4′-chlorobiphenyl (INTERMEDIATE 9, 12 g, 44.85 mmol) in THF (220 ml) under nitrogen, at −78° C. The resulting colored mixture was stirred at −78° C. for 30 minutes and a solution of tert-butyl 4-formylpiperidine-1-carboxylate (10.04 g, 47.09 mmol) in THF (15 ml) was added. The reaction mixture was allowed to warm to 0° C. during 3 hours and then was quenched with a solution of saturated aq. NH4Cl. The aqueous layer was extracted with ethyl acetate (3×) and the combined organic extracts and dried over MgSO4. The mixture was filtered and evaporation of the volatiles under reduced pressure gave a residue, which was purified by column chromatography (ISCO, 330 g silica gel column, eluting with 0→40% EtOAc/hexanes) to give tert-butyl 4-[(4′-chlorobiphenyl-2-yl)(hydroxy)methyl]piperidine-1-carboxylate as a mixture of enantiomers.

Workup

  1. temperatureto warm to 0° C. during 3 hours
  2. customwas quenched with a solution of saturated aq. NH4Cl
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×)
  4. dry with materialthe combined organic extracts and dried over MgSO4
  5. filtrationThe mixture was filtered
  6. customevaporation of the volatiles under reduced pressure
  7. customgave a residue, which
  8. customwas purified by column chromatography (ISCO, 330 g silica gel column, eluting with 0→40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-da1094dafe094154bb482550577a5906
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

Loading…