4-Bromo-1,2-dichlorobenzene → tert-Butyl 4-(3,4-dichlorophenyl)-4-hydroxypiperidine-1-carboxylate

HRID 1016128Notes

Reaction equation

HRID 1016128 reaction equation
[Li]CCCC.Br[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[C:9]([Cl:14])[CH:8]=1.[O:15]=[C:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1>C1COCC1>[Cl:14][C:9]1[CH:8]=[C:7]([C:16]2([OH:15])[CH2:17][CH2:18][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])[CH2:20][CH2:21]2)[CH:12]=[CH:11][C:10]=1[Cl:13]

Participants

5

Reactant 3

HCID 290134-Bromo-1,2-dichlorobenzeneHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418339Butyllithium

Product 1

HCID 49760236tert-Butyl 4-(3,4-dichlorophenyl)-4-hydroxypiperidine-1-carboxylateYield 97.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

n-BuLi (2.5 M, 2 mL, 5.21 mmol) was added into a solution of 4-bromo-1,2-dichlorobenzene (1.07 g, 4.74 mmol) in dry THF (10 mL) at −78° C. The mixture was stirred for 20 mins and then a solution of tert-butyl 4-oxopiperidine-1-carboxylate (0.95 g, 4.74 mmol) in THF (5 mL) was added. The mixture was further stirred at −78° C. for 1 h. After this time, the reaction was quenched with NH4Cl (aq., 15 mL), extracted with ethyl acetate (50 mL×3), dried over Na2SO4 and concentrated to yield a residue. The residue was purified by flash chromatography using 10-30% ethyl acetate in hexanes as an eluent to provide tert-butyl 4-(3,4-dichlorophenyl)-4-hydroxypiperidine-1-carboxylate (1.6 g, 90% purity, 88% yield) as a colorless oil. MS found: 346.3 (M+).

Workup

  1. stirringThe mixture was further stirred at −78° C. for 1 h
  2. customAfter this time, the reaction was quenched with NH4Cl (aq., 15 mL)
  3. extractionextracted with ethyl acetate (50 mL×3)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customto yield a residue
  7. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-0c111b279ac64fc19d12d38b95f14b4c
Source dataset
uspto-grants-2011_07
Patent number
US07985861B2

Reaction notes

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