Dichloromethane → 5-(2',6'-Dichlorobenzyloxy)-4-hydroxy-3-nitropentanoic acid t-butyl ester

HRID 634917Notes

Reaction equation

HRID 634917 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=[O:3].ClCC(O[CH2:12][C:13]1[C:18]([Cl:19])=[CH:17][CH:16]=[CH:15][CH:14]=1)O.C(N(CC)CC)C.[N+:27]([CH2:30][CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])([O-:29])=[O:28].C(Cl)[Cl:40]>CS(C)=O>[Cl:19][C:18]1[CH:17]=[CH:16][CH:15]=[C:14]([Cl:40])[C:13]=1[CH2:12][O:3][CH2:2][CH:1]([OH:5])[CH:30]([N+:27]([O-:29])=[O:28])[CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33]

Participants

7

Reactant 5

HCID 6344Dichloromethane2×HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 11095139Tert-butyl 3-nitropropionateHCID 695256972,6-Dichlorobenzyloxyethanol

Product 1

HCID 542726345-(2',6'-Dichlorobenzyloxy)-4-hydroxy-3-nitropentanoic acid t-butyl esterYield 74%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
-78 °C

Procedure

DMSO was added dropwise to a solution of (47.5 mL) oxalyl chloride (7.5 mL, 15.0 mmol, 2.0 M in methylene chloride) and the resultant reaction mixture was stirred for 10 min at −78° C. 2,6-Dichlorobenzyloxy-ethanol (2211 mg, 10 mmol) in dry methylene chloride (5 mL) was added dropwise to the mixture and the mixture was then stirred for 15 minutes under a nitrogen atmosphere at −78° C. Triethylamine (8.4 mL, 60 mmol) was added dropwise to the reaction mixture and the resultant mixture was stirred for 10 min at −78° C., then allowed to warm to 0° C. (over a period of approximately 20 min). A methylene chloride solution of tert-butyl 3-nitropropionate (1927 mg, 11.0 mmol in 5 ml of dry methylene chloride) was added dropwise to the reaction mixture and the mixture was stirred for 1 hour. The residue was extracted with ether and the resultant white solid was collected by filtration. The organic filtrate was washed with 5% KHSO4 solution (2×) and brine, dried over sodium sulfate, and concentrated to give a crude oil (3.95 g). The oil was subjected to flash chromatography on silica gel with ethyl acetate/hexanes (1:2) to afford the title product as a yellow oil (2.917 g, 74%). TLC (ethyl acetate, hexanes, 60/40): Rf=0.54.

Workup

  1. customthe resultant reaction mixture
  2. stirringthe mixture was then stirred for 15 minutes under a nitrogen atmosphere at −78° C
  3. temperatureto warm to 0° C. (over a period of approximately 20 min)
  4. stirringthe mixture was stirred for 1 hour
  5. extractionThe residue was extracted with ether
  6. filtrationthe resultant white solid was collected by filtration
  7. washThe organic filtrate was washed with 5% KHSO4 solution (2×) and brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customto give a crude oil (3.95 g)

Sources & evidence

ORD record
ord-d7508829c59a41f8853516c50d7b723c
Source dataset
uspto-grants-2001_02
Patent number
US06184244B2

Reaction notes

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