chloromethyl octanoate

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

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

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

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

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

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A heterogeneous solution of Cs2CO3 (2.60 g, 4.00 mmol), NaI (30 mg, 0.20 mmol) and nonanedioic acid (0.75 g, 4.00 mmol) in THF (20 ml) was stirred for ½ hour at 60° C. Chloromethyl octanoate (1.53 g, 8.00 mmol) in THF (5 ml) was added dropwise added to the solution and stirred at 60° C. for 48 hours. The reaction mixture was cooled to room temperature and evaporated in vacuo. Diethyl ether (20 ml) was added and the residue was washed with saturated NaHCO3 (3×15 ml), dried with MgSO4 and filtered. Evaporation in vacuo gave the product as a colourless oil (0,95 g, 47.9%). 1H-NMR (CDCl3) δ 5.76 (s, 4H), 2.37 (t, 8H), 1.65 (t, 8H), 1.30 (s br, 22H), 90 (t, 6H). 13C-NMR (CDCl3) δ 172.89, 62.32, 79.44, 34.35, 34.26, 31.99, 29.32, 29.23, 29.14, 24.99, 24.86, 22.94, 14.41. added to the solution The reaction mixture was cooled to room temperature evaporated in vacuo Diethyl ether (20 ml) was added the residue was washed with saturated NaHCO3 (3×15 ml) dried with MgSO4 filtered Evaporation in vacuo

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

Procedure: To a round bottomed flask equipped with a reflux condenser and a stirring bar were added piroxicam (1.00 g, 3.0 mmol), potassium carbonate (840 mg, 6.0 mmol), chloromethyl octanoate (870 mg, 4.5 mmol) and acetone (15 mL). The heterogenous reaction mixture was heated to reflux under a nitrogen atmosphere. After 6 hours additional chloromethyl octanoate (250 mg, 0.75 mmol) and additional potassium carbonate (210 mg, 1.5 mmol) were added and reflux continued for an additional hour. Chromatographed title product was isolated, according to the method of Example 5, as a yellow foam which oiled from toluene/hexane, but crystallized from the oil upon refrigeration (690 mg white crystals, 1.4 mmol, 47%); mp 98°-99° C.; IR (KBr) 1766, 1683 cm-1 ; 1H NMR (CDCl3) delta 0.87 (t, J=8 Hz, 3H), 1.02-1.48 (m, 10H), 2.19 (t, J=6 Hz, 2 H), 3.12 (s, 3H), 5.70 (s, 2H), 7.08-7.17 (m, 1H), 7.67-7.98 (m, 5H), 8.30-8.45 (m, 2H), 9.32 (br s, 1H); precise mass calcd for C24H30N3O6S m/e (P+ +H) 488.1859, found 488.1794. To a round bottomed flask equipped with a reflux condenser and a stirring bar The heterogenous reaction mixture was heated to reflux under a nitrogen atmosphere reflux continued for an additional hour Chromatographed title product was isolated crystallized from the oil upon refrigeration (690 mg white crystals, 1.4 mmol, 47%)

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 4-methylphenylacetic acid (2.27 g, 15.15 mmol), sodium hydrogen carbonate (5.09 g, 60.6 mmol) and tetra-n-butylammonium hydrogen sulfate (0.51 g, 1.52 mmol) in water-dichloromethane (62.5 mL, 1:1 v/v) and chloromethylchlorosulfate (2.50 g, 15.15 mmol) in dichloromethane (7.5 mL), at room temperature for 18 h. Purification by flash chromatography (hexane/ethyl acetate 9:1) afforded 322 as a colourless oil (2.42 g, 12.18 mmol, 80%). Purification by flash chromatography (hexane/ethyl acetate 9:1)

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:; See reaction.notes.procedure_details.

Procedure: Compound 43 was prepared by a procedure similar to that of Harada and co-workers (Harada, N. et al. Synth. Commun. 1995, 25, 767-772). To a vigorously stirring solution of octanoic 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) at 0° C. was added chloromethylchlorosulfate (5.15 g, 31.2 mmol) in dichloromethane (15 mL), and the reaction stirred at room temperature for a further 18 h. The mixture was diluted with dichloromethane (150 mL) and washed with brine (150 mL), dried over anhydrous magnesium sulfate and the solvent removed in vacuo. Purification by flash chromatography (hexane/ethyl acetate 9:1) afforded 43 as a yellow oil (5.28 g, 27.3 mmol, 88%). 1H NMR (400 MHz, CDCl3) δ 0.86-0.90 (3H, m, Me), 1.24-1.37 (8H, m, CH3(CH2)4), 1.60-1.71 (2H, m, CH2CH2COO), 2.36-2.40 (2H, m, CH2CH2COO), 5.71 (2H, s, CH2Cl). Compound 43 was prepared by a procedure similar to that of Harada and co-workers (Harada, N. et al. Synth. Commun. 1995, 25, 767-772) washed with brine (150 mL) dried over anhydrous magnesium sulfate the solvent removed in vacuo Purification by flash chromatography (hexane/ethyl acetate 9:1)

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

Procedure: (1S,2S,3S,5R,6S)-3′-((Allyloxy)carbonyl)-3-fluoro-5′-oxospiro[bicyclo[3.1.0]hexan-2,4′-oxazolidine]-6-carboxylic acid (A-1-2, 300 mg) and chloromethyl octanoate (483 mg) were treated in the same manner as in Example A-1 (3) and (4) to give the title compound (A-6, 95 mg) as a colorless solid.

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