Triethylamine → HCID 86005167, compound

HRID 2376665Notes

Reaction equation

HRID 2376665 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([OH:13])=[O:12])=[C:6]([Cl:14])[CH:5]=1)(=[O:3])[CH3:2].C(N(CC)CC)C.[N+:22]([C:25]1[CH:32]=[CH:31][C:28]([CH2:29]Br)=[CH:27][CH:26]=1)([O-:24])=[O:23]>CN(C=O)C>[C:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([O:13][CH2:29][C:28]2[CH:31]=[CH:32][C:25]([N+:22]([O-:24])=[O:23])=[CH:26][CH:27]=2)=[O:12])=[C:6]([Cl:14])[CH:5]=1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 660114-Nitrobenzyl bromideHCID 23106770HCID 23106770, compound

Product 1

HCID 86005167HCID 86005167, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 4-acetyl-2-chlorophenylacetic acid (2.65 g, 12.5 mmol) in DMF solution (26 mL) were added triethylamine (3.5 ml, 25 mmol) and 4-nitrobenzyl bromide (5.4 g, 25mol), and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was added to an ice cooled saturated potassium hydrogencarbonate solution, the organic layer was separated by a separatory funnel, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined and dried over sodium sulfate, filtered and concentrated. The residue was purified with silica gel chromatography (silica gel 180 ml, hexane:EtOAc=2:1→1:1) to give 4-nitrobenzyl (4-acetyl-2-chlorophenyl)acetate (3.56 g, yield, 82%) as white crystals. The product was subjected to next reaction without further purification. To 4-nitrobenzyl(4-acetyl-2-chlorophenyl)acetate (3.56 g, 11.4 mmol) and triethylamine (2.0 ml, 15.9 mmol) in dichloromethane (36 ml) was dropped at 0° C. under stirring trifluoromethanesulfonic acid trimethylsilyl ether (2.4 ml, 14.8 mmol), and the mixture was stirred for 20 minutes. To the reaction mixture were added at 0° C. dichloromethane (50 mL), (2R,3R)-3-((1R)-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-4-oxo-2-azetidinyl acetate (4.6 g, 15.9 mmol), and zinc iodide (2.2 g, 6.8 mmol), and then the ice bath was removed. The mixture was stirred at room temperature for 4.5 hours and then added to an ice cooled saturated potassium hydrogencarbonate solution. The organic layer was separated by a separatory funnel and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, dried over sodium sulfate, filtered, and concentrated. The residue was purified with silica gel chromatography (silica gel 180 ml, hexane:EtOAc=4:1→0:1) to give 4-nitrobenzyl(4-{[(2R,3S)-3-((1R)-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-4-oxoazetidin-2-yl]acetyl}-2-chlorophenyl)acetate (5.2 g, yield 79.7%) as a white solid.

Workup

  1. customthe organic layer was separated by a separatory funnel
  2. extractionthe aqueous layer was extracted with ethyl acetate
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified with silica gel chromatography (silica gel 180 ml, hexane:EtOAc=2:1→1:1)

Sources & evidence

ORD record
ord-79382f6f85f64e71b6c30acc3de63fe0
Source dataset
uspto-grants-2008_12
Patent number
US07468364B2

Reaction notes

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