Phenoxyacetyl chloride

Phenoxyacetyl chloride [701-99-5] M 170.6, b 112°/10mm, 102°/16mm, 225-226°/atm, d 1.235, Dp 1.534. If it has no OH band in the IR then distil in a vacuum, taking precutions for the moisture-sensitive copound. If it contains free acid (due to hydrolysis, OH bands in the IR) then add an equal volume of redistilled SOCI2, reflux for 2-3h, evaporate and distil the residue is a vacuum as before. The amide has m 101°. [McElvain and Carney JACS 68 2592 7946]. 

Reaction of Schiff bases 422 with a mixture of phosphorus oxychloride and dichloroacetic acid in DMF gave triazolopyrimidinones (423) instead of the expected 3,3-dichloroazetidinones (424) (88JHC173). 1,4-Cycloaddition of 422 (R = SMe R1 = Ph) with phenoxyacetyl chloride in the presence of triethylamine gave the dihydro-1,2,4-triazolo[4,3-ajpyrimidinone 425 (88JHC173) (Scheme 82). 

In the course of their studies on the synthesis of ot-amido-spiro-(5-lactams as analogs of penicillin and cephalosporin, Manhas et al. [76] have prepared 1-phenyl-3-phenoxy-4,4-spirocyclohexylazetidin-2-ones by the reaction of phenoxyacetyl chloride 7 and cyclohexylidenephenylamine 8 in the presence of triethylamine and dichloromethane. Azidoacetyl chloride was found to be even more reactive... 

Scheme 3 Preparation of spiro-[S-lactams using of phenoxyacetyl chloride and cyclohexylidenephenylamine...

A benzothiazepine-fused (3-lactam library has been reported to be obtained [106] via Staudinger cycloaddition of 2,3- dihydro-1,5-benzothiazepines and various acyl chlorides such as phthalimidoacetyl chloride (path a, Scheme 35), chloroacetyl chloride (path b, Scheme 35), dichloroacetyl chloride (path c, Scheme 35), and phenoxyacetyl chloride (path d, Scheme 35). 

Scheme 45 Synthesis of 4-phenoxymethylene-P-lactam from (4-methyloxyphenyl)azides and phenoxyacetyl chloride...

A one-pot cascade approach to 4-alkylidene-(3-lactams from aryl azides and aryloxyacetyl chlorides has been reported. (4-Methyloxyphenyl)azides reacted with triphenylphosphine in 1,2-dichloroethane to form triphenylphosphazene, which was treated with phenoxyacetyl chloride and Et3N to afford 4-phenoxy-methylene-(3-lactam (Scheme 45), [122]. 

In a similar way, formation and subsequent hydrolysis of bis-p-lactams provide a route to peripheral functionalization of macrocyclic imines. For example, racemic bis-p-lactam 15, Scheme 5, which is formed upon Staudinger reaction of imine 14 and the ketene originated from phenoxyacetyl chloride and triethylamine, led to C2 symmetric amino acid 16 in high yield [59]. 

Resin bound amines 26 were condensed with ort/io-nitrobenzaldehyde in dichloromethane in the presence of anhydrous sodium sulfate as drying agent to furnish the imines 27. Cycloaddition [2 + 2] of 27 with ketene was carried out in dichloromethane at —78°C. The ketene was generated in situ from corresponding phenoxyacetyl chloride in the presence of triethylamine. In all cases, c/s-p-lactams... 

Amino-3-hydroxy-5-t-butyloxycarbonylamino-l,6-diphenylhexanesuccinate (111.9 g, 0.25 mol) was charged to a 2-L 3-necked flask with mechanical stirring. NaHC03 (106 g, 1.26 mol), 600 ml H20 and 600 ml EtOAc were added and stirred until solids were dissolved (15 min). A solution of the 2,6-dimethyl-phenoxyacetyl chloride and EtOAc (100 ml) was added. After 30 min starting materials were consumed (HPLC analysis) and the layers were separated. The aqueous layer was extracted with EtOAc, the organic layers were combined and washed with 200 ml of 1 M NaOH, 200 ml of 10% HCI, 200 ml of brine, dried over MgS04, filtered and concentrated to provide (2S,3S,5S)-2-(2,6-dimethylphenoxyacetyl)amino-3-hydroxy-5-(t-butyloxycarbonylamino)-l,6-diphenylhexane as a white solid. 

Enantiopure fused oxopiperazino-/3-lactams have been produced by application of the Staudinger reaction with 5,6-dihydropyrazin-2-(l/7)-ones and the /3-lactams were converted to the 2-oxopiperazine-3-acetic acid esters in good yield with no epimerization (Equation 86) <2006TL8911>. Fused /3-lactams have been formed from macrocyclic imines by use of the Staudinger reaction (see Section 2.04.9.7). When phenoxyacetyl chloride and triethylamine were used, the best yields (45-52%) of the fused /3-lactams were obtained with dry dichloromethane as solvent <2006TL8855>. 

The resin was shaken for a further 2 x 30 min with benzylamine (2 x 85 iL) in CH2CI2 (2x3 mL) until IR showed the disappearance of the aldehyde carbonyl stretch. After draining, the resin was washed with CH2CI2 (3x 2 ml). To the resin was added anhydrous CH2CI2 (3 mL), and the mixture was cooled to 0 °C. EtsN (200 pL, 1.43 mmol) was added, followed by the dropwise addition of phenoxyacetyl chloride (100 pL, 0.72 mmol). The resin was agitated for 30 min at 0 °C, allowed to warm to r. t. and shaken for 18 h. The resin was then drained and washed as follows ... 

Conversion of 64 with benzylamine, followed by phenoxyacetyl chloride gave immobilized P-lactam 65. The product 66 was detached from the resin by cleavage of the N,O-acetal with trifluoroacetic acid and was obtained in 75% yield (Scheme 12.27). 

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