Benzyl Bromide → 1-(t-Butoxycarbonyl)-4-(3-phenyl-2,2-bis(carboethoxy)propyl)piperidine

HRID 1386713Notes

Reaction equation

HRID 1386713 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH:15]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:36](Br)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([CH2:14][C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 21180611Diethyl {[1-(tert-butoxycarbonyl)piperidin-4-yl]methyl}propanedioate

Product 1

HCID 211806581-(t-Butoxycarbonyl)-4-(3-phenyl-2,2-bis(carboethoxy)propyl)piperidineYield 96.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 628 mg (1.76 mmol) of 1-(t-butoxycarbonyl)-4-(2,2-bis(carbethoxy)ethyl)piperidine (from EXAMPLE 32, Step B) in 8 mL of THF at 0° C. was treated with 2.0 mL of 1.0 M sodium bis(trimethylsilyl) amide solution in THF and stirred cold for 10 min. The resulting mixture was treated with 0.35 mL (2.9 mmol) of benzyl bromide then warmed to rt and stirred for 1 h. The reaction was quenched with 10 mL of sat'd NH4Cl and the quenched mixture was partitioned between 50 mL of ether and 25 mL of H2O. The layers were separated and the organic layer was washed with 25 mL of sat'd NaCl, dried over MgSO4 and concentrated. Flash chromatography on 30 g of silica gel using 4:1 v/v hexanes/ether afforded 760 mg (96%) of the title compound: 1H NMR (500 MHz) δ 1.08-1.16 (m, 2H), 1.23 (t, J=7.0,66H), 1.45 (s, 9H), 1.54-1.58 (m, 2H), 1.60-1.66 (m, 1H), 1.78 (d, J=6.0, 2H), 2.68 (app t, J=11.5, 21), 3.28 (s, 2H), 4.01 (br s, 2H), 4.15 (q, J=7.0, 4H), 7.06-7.25 (5H).

Workup

  1. stirringstirred for 1 h
  2. customThe reaction was quenched with 10 mL of sat'd NH4Cl
  3. customthe quenched mixture was partitioned between 50 mL of ether and 25 mL of H2O
  4. customThe layers were separated
  5. washthe organic layer was washed with 25 mL of sat'd NaCl
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-e93333eda1244a4d976d54edcf3ff960
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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