1-Chloro-4-(chloromethyl)benzene → 1-tert-Butyl 4-ethyl 4-[(4-chlorophenyl)methyl]piperidine-1,4-dicarboxylate

HRID 2259923Notes

Reaction equation

HRID 2259923 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[CH:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1)[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:29][C:30]1[CH:37]=[CH:36][C:33]([CH2:34]Cl)=[CH:32][CH:31]=1>O1CCCC1>[CH2:1]([O:3][C:4](=[O:18])[C:5]1([CH2:34][C:33]2[CH:36]=[CH:37][C:30]([Cl:29])=[CH:31][CH:32]=2)[CH2:6][CH2:7][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:9][CH2:10]1)[CH3:2]

Participants

5

Reactant 3

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 2733832Lithium HexamethyldisilazideHCID 27588121-Tert-butyl 4-ethyl piperidine-1,4-dicarboxylate

Product 1

HCID 162182741-tert-Butyl 4-ethyl 4-[(4-chlorophenyl)methyl]piperidine-1,4-dicarboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of ethyl-N-boc-isonipecotate (51.4 g, 0.2 mole) in tetrahydrofuran (1 L) at -78° C. was treated with a solution of lithium bis (trimethylsilyl)amide in tetrahydrofuran (220 mL of a 1M solution). The solution was stirred at -60° for 15 minutes at which time 4-chlorobenzyl chloride (33.8 g, 0.22 moles) was added and the reaction warmed to room temperature over 1.5 hours. The reaction was concentrated at reduced pressure to one quarter volume and then poured into saturated aqueous sodium bicarbonate (1 L) and extracted with ethyl acetate (2×800 mL). The combined organic extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated at reduced pressure. The residue was chromatographed on silica gel with 30% ethyl acetate/hexane as eluent to give 61.3 g.

Workup

  1. additionwas added
  2. concentrationThe reaction was concentrated at reduced pressure to one quarter volume
  3. additionpoured into saturated aqueous sodium bicarbonate (1 L)
  4. extractionextracted with ethyl acetate (2×800 mL)
  5. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated at reduced pressure
  8. customThe residue was chromatographed on silica gel with 30% ethyl acetate/hexane as eluent
  9. customto give 61.3 g

Sources & evidence

ORD record
ord-dee33001814c44cc9ea66cc8a9806c47
Source dataset
uspto-grants-1995_12
Patent number
US05475109

Reaction notes

Loading…