Benzyl Bromide → Ethyl-N-Benzenesulfonyl-4-(benzyl)-piperidine-4-carboxylate

HRID 53238Notes

Reaction equation

HRID 53238 reaction equation
[CH2:1]([O:3][C:4](=[O:20])[CH:5]1[CH2:10][CH2:9][N:8]([S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])[CH2:7][CH2:6]1)[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:31](Br)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>O1CCCC1>[CH2:1]([O:3][C:4]([C:5]1([CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH2:10][CH2:9][N:8]([S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:12])=[O:13])[CH2:7][CH2:6]1)=[O:20])[CH3:2]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 257103Ethyl 1-(phenylsulfonyl)piperidine-4-carboxylateHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 19962183Ethyl-N-Benzenesulfonyl-4-(benzyl)-piperidine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of ethyl-N-benzenesulfonyl-isonipecotate (5 g, 0.016 mole) in tetrahydrofuran (1 L) at -78° C. was treated with a solution of Lithium bis (trimethylsilyl)amide in tetrahydrofuran (18.5 mL of a 1M solution). The solution was stirred at -60° for 15 minutes at which time benzyl bromide (3.15 g, 0.016 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 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 5.1 g. 1H NMR CDCl3 δ 7.7 (d,=8.5 Hz, 2H), 7.6-7.4 (m, 3H), 7.3-7.2 (m, 3H), 7.1-7.0 (m, 2H), 3.98 (q, J=7 Hz, 2H), 3.65 (m, 2H), 2.78 (s, 2H), 2.35 (dt, J=2.5, 12 Hz, 2H), 2.19 (d, J=12 Hz, 2H), 1.61 (dt, J=4.5, 12 Hz, 2H).

Workup

  1. additionwas added
  2. concentrationThe reaction was concentrated at reduced pressure
  3. additionpoured into saturated aqueous sodium bicarbonate (1 L)
  4. extractionextracted with ethyl acetate (2×800 mL)
  5. dry with materialThe combined 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 5.1 g

Sources & evidence

ORD record
ord-35ba0c302e22404ab0f9a6d742009670
Source dataset
uspto-grants-1997_04
Patent number
US05618830

Reaction notes

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