Ethyl diazoacetate → 1-Boc-4-ethoxycarbonylmethoxypiperidine

HRID 366238Notes

Reaction equation

HRID 366238 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N+](=[CH:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])=[N-]>ClC(Cl)C.C([O-])(=O)C.[Rh+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 12192Ethyl diazoacetateHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 105173911-Boc-4-ethoxycarbonylmethoxypiperidineYield 47.3%

Reagents, catalysts & solvents 2

HCID 21674Acetic acid, rhodium(2+) saltCatalystHCID 63651,1-DichloroethaneSolvent2×

Procedure

To a solution of 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (5.0 g, 25 mmol) and rhodium(II)acetate (180 mg) in 500 ml dichloroethane at 80° C. was added (over 90 min) ethyl diazoacetate (4.2 ml, 50 mmol) in 220 ml dichloroethane. The mixture was stirred for 7 h and quenched with aqueous sodium bicarbonate (2×100 ml). The organic phase was isolated and washed with brine (2×100 ml), dried over magnesium sulfate and concentrated in vacuo. The crude product was chromatographed on silica (80g) in petroleum ether:ethyl acetate (4:1) to give 3.4 g of 4-(ethoxycarbonylmethoxy)piperidine-1-carboxylic acid tert-butylester. The product was taken up in 40 ml of a 1 M lithium hydroxide solution in water:methanol (1:3) and stirred for 60 min. The mixture was concentrated in vacuo and dissolved in 20 ml of water, acidified to pH 4 with 1 M aqueous hydrogen chloride and extracted with ethyl acetate (3×30 ml). The combined organic layers were washed with brine (10 ml), dried over magnesium sulfate and concentrated in vacuo to give 1.79 g of 4-(carboxymethoxy)piperidine-1-carboxylic acid tert-butyl ester.

Workup

  1. customquenched with aqueous sodium bicarbonate (2×100 ml)
  2. customThe organic phase was isolated
  3. washwashed with brine (2×100 ml)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was chromatographed on silica (80g) in petroleum ether:ethyl acetate (4:1)

Sources & evidence

ORD record
ord-e8b706f6d08542ecad13f9094556ccd5
Source dataset
uspto-grants-2000_10
Patent number
US06127391

Reaction notes

Loading…