Benzyl Bromide → tert-Butyl 3-[3-(Benzyloxy)propyl]pyrrolidine-1-carboxylate

HRID 2095394Notes

Reaction equation

HRID 2095394 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[CH2:14][CH2:13][CH:12]([CH2:15][CH2:16][CH2:17][OH:18])[CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH2:19](Br)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1COCC1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:19]([O:18][CH2:17][CH2:16][CH2:15][CH:12]1[CH2:13][CH2:14][N:10]([C:8]([O:7][C:3]([CH3:6])([CH3:5])[CH3:4])=[O:9])[CH2:11]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 59371373HCID 59371373, compound

Product 1

HCID 59371609tert-Butyl 3-[3-(Benzyloxy)propyl]pyrrolidine-1-carboxylateYield 87%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

NaH (0.92 g, 38 mmol, 1.7 equiv.) was added to a solution of 3-[1-(tert-butoxycarbonyl)-3-pyrrolidinyl]-1-propanol (5.11 g, 22.3 mmol) in anhydrous THF (180 mL) at 0° C. under N2. The mixture was warmed to room temperature and stirred for about 2 h. Then benzyl bromide (3.2 mL, 26.9 mmol, 1.2 equiv.) and tetra-n-butylammonium bromide (0.72 g, 2.2 mmol, 0.10 equiv.) were added at room temperature. The solution was stirred for 20 h at room temperature, after which time period the reaction was completed as judged by TLC analysis (SiO2, EtOAc/petroleum ether 1:10). The reaction was then quenched by the addition of 20 mL of saturated aqueous NH4Cl solution. The product was extracted into EtOAc (3×60 mL), and the combined organic layers were washed with brine. After concentration in vacuo, the residue was applied onto a silica gel column, which was eluted with EtOAc/petroleum ether 1:20-1:10 to provide the product (6.20 g, 87%) as a colorless oil. 1H NMR (CDCl3, 300 MHz) δ 7.30-7.37 (m, 5H), 4.52 (s, 2H), 3.42-3.57 (m, 4H), 3.23-3.30 (m, 1H), 2.89 (dd, 1H, J=10.5, 8.7 Hz), 2.06-2.12 (m, 1H), 1.96-2.01 (m, 1H), 1.61-1.69 (m, 2H), 1.47-1.51 (m, 3H), 1.48 (s, 9H).

Workup

  1. stirringThe solution was stirred for 20 h at room temperature
  2. customThe reaction was then quenched by the addition of 20 mL of saturated aqueous NH4Cl solution
  3. extractionThe product was extracted into EtOAc (3×60 mL)
  4. washthe combined organic layers were washed with brine
  5. concentrationAfter concentration in vacuo
  6. washwas eluted with EtOAc/petroleum ether 1:20-1:10

Sources & evidence

ORD record
ord-b5a7c3c441bc4dd88e472a459677207c
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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