Ethyl diazoacetate → HCID 10803196, compound

HRID 365424Notes

Reaction equation

HRID 365424 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][C@H:9]1[CH2:10][OH:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:15]([O:17][C:18](=[O:22])[CH:19]=[N+]=[N-])[CH3:16]>ClCCCl>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][C@H:9]1[CH2:10][O:11][CH2:19][C:18]([O:17][CH2:15][CH3:16])=[O:22])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 12192Ethyl diazoacetate2×HCID 643448(S)-(-)-N-Boc-prolinol

Product 1

HCID 10803196HCID 10803196, compoundYield 65.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent3×

Conditions

Temperature
80 °C

Procedure

To a solution of N-t-butyloxycarbonyl-(S)-prolinol (5.0 g, 25 mmol) in 1,2-dichloroethane (500 ml) rhodium(II)acetate (180 mg) was added and the mixture was heated to 80° C. Ethyldiazoacetate (3.9 ml, 37 mmol) in 1,2-dichloroethane (180 ml) was added over a period of 90 min and the mixture was heated at 80° C. for 3 hours. Then another portion of ethyl diazoacetate (1.3 ml, 12 mmol) in 1,2-dichloroethane (40 ml) was added and the mixture was refluxed for 6 hours. The mixture was cooled to room temperature and washed with saturated sodium bicarbonate (2×100 ml) and brine (100 ml), dried (magnesium sulfate) and concentrated in vacuo. The crude product was chromatographed on silica (300 g) with petrol ether/ethyl acetate 4:1 as eluent to give 4.7 g of (2S)-2-(((ethoxycarbonyl)methoxy)methyl)pyrrolidin-1-carboxylic acid tert-butylester. The obtained product was dissolved in 1 M lithium hydroxide in water/methanol 1:3 (50 ml) and stirred at room temperature overnight. The mixture was concentrated in vacuo, water (20 mL) was added and washed with ether (20 mL). The aqueous phase was acidified to pH 4 with 1 M aqueous hydrogen chloride, extracted with ethyl acetate (2×100 ml) and the combined organic layers were dried (magnesium sulfate) and concentrated in vacuo to give 3.6 g of (2S)-2-(((carboxy)methoxy)methyl)-pyrrolidin-1-carboxylic acid tert-butyl ester.

Workup

  1. temperaturethe mixture was heated at 80° C. for 3 hours
  2. temperaturethe mixture was refluxed for 6 hours
  3. temperatureThe mixture was cooled to room temperature
  4. washwashed with saturated sodium bicarbonate (2×100 ml) and brine (100 ml)
  5. dry with materialdried (magnesium sulfate)
  6. concentrationconcentrated in vacuo
  7. customThe crude product was chromatographed on silica (300 g) with petrol ether/ethyl acetate 4:1 as eluent

Sources & evidence

ORD record
ord-25744339dfe54fff862d0e52ef9cb003
Source dataset
uspto-grants-2000_10
Patent number
US06127341

Reaction notes

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