1-Chloro-4-(chloromethyl)benzene → Ethyl-3-(4-chlorobenzyl)-N-Boc-piperidin-3-caroxylate

HRID 2259926Notes

Reaction equation

HRID 2259926 reaction equation
[CH2:1]([O:3][C:4](=[O:18])[CH:5]1[CH2:10][CH2:9][CH2:8][N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[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.C(=O)(O)[O-].[Na+]>O1CCCC1>[CH2:1]([O:3][C:4]([C:5]1([CH2:34][C:33]2[CH:36]=[CH:37][C:30]([Cl:29])=[CH:31][CH:32]=2)[CH2:10][CH2:9][CH2:8][N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6]1)=[O:18])[CH3:2]

Participants

6

Reactant 4

HCID 77231-Chloro-4-(chloromethyl)benzeneHCID 3577271-Tert-butyl 3-ethyl piperidine-1,3-dicarboxylateHCID 516892Sodium BicarbonateHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 19962177Ethyl-3-(4-chlorobenzyl)-N-Boc-piperidin-3-caroxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of ethyl-N-boc-nipecotate (45 g, 0.18 mole) in tetrahydrofuran (200 mL) at -40° C. was treated with a solution of lithium bis (trimethylsilyl)amide in tetrahydrofuran (320 mL of a 1M solution). The solution was stirred at -40° for 15 minutes at which time 4-Chlorobenzyl chloride (34.59 g, 0.215 moles) was added and the reaction warmed to room temperature over 1.5 hours. The reaction was poured into saturated aqueous sodium bicarbonate (1 L) and extracted with ethyl acetate (3×500 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 36.5 g.

Workup

  1. additionwas added
  2. extractionextracted with ethyl acetate (3×500 mL)
  3. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated at reduced pressure
  6. customThe residue was chromatographed on silica gel with 30% ethyl acetate/hexane as eluent
  7. customto give 36.5 g

Sources & evidence

ORD record
ord-705351222da34a7fab91f46ec8ed53c7
Source dataset
uspto-grants-1995_12
Patent number
US05475109

Reaction notes

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