Benzyl Bromide → 1-tert-Butyl 3-ethyl 3-benzylpiperidine-1,3-dicarboxylate

HRID 970407Notes

Reaction equation

HRID 970407 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si](C)(C)[N-][Si](C)(C)C.[Na+].[CH2:29](Br)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>C1COCC1.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([C:14]([O:16][CH2:17][CH3:18])=[O:15])([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 3577271-Tert-butyl 3-ethyl piperidine-1,3-dicarboxylateHCID 2724254Sodium bis(trimethylsilyl)amide

Product 1

HCID 196965021-tert-Butyl 3-ethyl 3-benzylpiperidine-1,3-dicarboxylateYield 56.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of N-(t-butoxycarbonyl)-3-(carboethoxy)-piperidine (800 mg, 3.11 mmol) in dry THF (10 mL) at −78° C. was added a 0.6M solution of sodium hexamethyldisilazide in toluene (5.7 mL). The reaction was stirred for 1 h when benzyl bromide (559 mg, 3.27 mmol) was added. After 1 h, the reaction was warmed to room temperature for 15 h. The reaction was quenched by the addition of 1M HCl (10 mL). The reaction was extracted with EtOAc (4×20 mL). The organic layers were combined, washed with brine, dried over Na2SO4, and conc. in vacuo to an oil. The oil was purified by flash chromatography (SiO2, 5–15% EtOAc in hexanes) to yield 606 mg of the product as a colorless oil. MS (ESI) 348 (M+H).

Workup

  1. additionwas added
  2. customThe reaction was quenched by the addition of 1M HCl (10 mL)
  3. extractionThe reaction was extracted with EtOAc (4×20 mL)
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. customThe oil was purified by flash chromatography (SiO2, 5–15% EtOAc in hexanes)

Sources & evidence

ORD record
ord-d0a9276b49e744e9974faf8d85b2c66c
Source dataset
uspto-grants-2007_12
Patent number
US07312222B2

Reaction notes

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