chloromethyl 2-phenylacetate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the general procedure for the preparation of acyloxyalkyl/alkoxycarbonyloxyalkyl carboxylic esters from carboxylic acids of Description 22, (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoic acid (11) (0.5 g, 1.3 mmol) dissolved in 10 mL of anhydrous toluene was reacted with 1.1 g (4.0 mmol) of chloromethyl 2-phenylacetate in the presence of 0.44 g (1.6 mmol) of silver carbonate (Ag2CO3). After work-up, the crude material was purified by silica gel column chromatography using a mixture of ethyl acetate (EtOAc) and hexane (Hxn) (EtOAc/Hxn=1:2) as eluent to provide 0.44 g (64% yield) of the title compound (28a) as a colorless oil. Rf=0.47 (EtOAc/Hxn=1:2). 1H NMR (400 MHz, CDCl3): δ=0.97 (s, 3H), 0.99 (s, 3H), 2.24-2.30 (m, 2H), 3.20-3.24 (m, 2H), 3.62-3.65 (m, 2H), 3.68 (s, 2H), 3.84 (s, 1H), 3.91 (d, J=9.2 Hz, 1H), 4.15 (d, J=9.6 Hz, 1H), 4.28 (d, J=10.8 Hz, 1H), 4.53 (d, J=11.2 Hz, 1H), 5.78 (d, J=5.6 Hz, 1H), 5.87 (d, J=5.6 Hz, 1H), 7.25-7.38 (m, 10H) ppm. MS (ESI) m/z 548.99 (M+Na)+. The analytical data was consistent with the proposed structure. After work-up, the crude material was purified by silica gel column chromatography a mixture of ethyl acetate (EtOAc) and hexane (Hxn) (EtOAc/Hxn=1:2) as eluent

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chloromethyl phenylacetate (Neuenschwander, Markus et. al., Helv. Chin. Acta, 61 (1978) 2047) (1.59 g. 8.6 mmol) in dry DMF (20 ml) is added dropwise at 50° C. to a solution of cesium 5-(N-acetylamino)-3-(N-acetyl-N-methylamino)-2,4,6-triiodobenzenecarboxylate (7.28 g, 9.6 mmol) and sodium iodide (64 mg, 0.42 mmol) in dry DMF (100 ml). The precipitate is removed by filtration after stirring for 20 hours and the solvent is removed at reduced pressure. The residue is dissolved in chloroform (200 ml) and washed twice with a saturated sodium hydrogen carbonate solution and twice with water. After drying with magnesium sulfate the solvent is removed at reduced pressure to give the title compound: The precipitate is removed by filtration the solvent is removed at reduced pressure The residue is dissolved in chloroform (200 ml) washed twice with a saturated sodium hydrogen carbonate solution and twice with water After drying with magnesium sulfate the solvent is removed at reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Chloromethyl phenylacetate (1.0 2 g, 5.5 mmol) (Intermediate 4) in dry DMF (50 ml) is added dropwise at 50° C. to a solution of cesium 5-(N-acetylamino)-3-(N-acetyl-N-methylamino)-2,4,6-triiodobenzenecarboxylate (3.80 g, 5.0 mmol) and sodium iodide (37 mg, 0.25 mmol) in dry DMF (70 ml). The precipitate is removed by filtration after stirring for 4 hours and the solvent is removed at reduced pressure. The residue is dissolved in chloroform (50 ml) and washed four times with a saturated sodium hydrogen carbonate solution. After drying with magnesium sulfate the solvent is removed at reduced pressure to give the title compound: The precipitate is removed by filtration the solvent is removed at reduced pressure The residue is dissolved in chloroform (50 ml) washed four times with a saturated sodium hydrogen carbonate solution After drying with magnesium sulfate the solvent is removed at reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A similar procedure (Harada, N. et al. Synth. Commun. 1995, 25, 767-772) to that described for the preparation of 43 was followed using phenylacetic acid (4.50 g, 31.2 mmol), sodium hydrogen carbonate (10.48 g, 124.8 mmol) and tetra-n-butylammonium hydrogen sulfate (1.06 g, 3.12 mmol) in water-dichloromethane (125 mL, 1:1 v/v) and chloromethylchlorosulfate (5.15 g, 31.2 mmol) in dichloromethane (15 mL), at room temperature for 18 h. Purification by flash chromatography (hexane/ethyl acetate 9:1) afforded 49 as a yellow oil (1.81 g, 9.82 mmol, 31%). Purification by flash chromatography (hexane/ethyl acetate 9:1)

Conditions: temp:0.00; pressure:0.00; stir: