1,1,1,2,2-pentafluoro-5-iodopentane

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: Starting with the (3S,4S)-7-methoxy-3-(4-methoxy-phenyl)-3-methyl-4-(2-propenyl)thiochroman prepared in Example 3 and ethyl 2-(4,4,5,5,5-pentafluoropentyl)-9-decenoate separately prepared from 1-iodo-4,4,5,5,5-pentafluoropentane, diethyl malonate and 1-iodo-7-octene, a procedure analogous to that as shown in Example 2 or 3 was repeated to give 11-[(3S,4S)-7-hydroxy-3-(4-hydroxyphenyl)-3-methylthiochroman-4-yl]-2-(4,4,5,5,5-pentafluoropentyl)undecanoic acid.

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

Procedure: Starting with the (3R,4R)-7-methoxy-3-(4-methoxy-phenyl)-3-methyl-4-(2-propenyl)thiochroman prepared in Example 2 and ethyl 2-(4,4,5,5,5-pentafluoropentyl)-9-decenoate separately prepared from 1-iodo-4,4,5,5,5-pentafluoropentane, diethyl malonate and 1-iodo-7-octene, a procedure analogous to that as shown in Example 2 or 3 was repeated to give 11-[(3R,4R)-7-hydroxy-3-(4-hydroxyphenyl)-3-methylthiochroman-4-yl]-2-(4,4,5,5,5-pentafluoropentyl)undecanoic acid.

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

Procedure: Ethyl 2-(4,4,5,5,5-pentafluoropentyl)-8-nonenoate was separately prepared from 1-iodo-4,4,5,5,5-pentafluoropentane, diethyl malonate and 1-iodo-6-heptene. A solution of this compound (4.55 g, 13.21 mmol), (3R,4R)-7-methoxy-3-(4-methoxyphenyl)-3-methyl-4-(2-propenyl)thiochroman (2.5 g, 7.342 mmol) and benzylidene-bis(tricyclohexylphosphine)dichlororuthenium (302 mg, 0.367 mmol) in dichloromethane (60 ml) was heated under reflux for 6 hours. After the reaction was completed, the solvent was distilled off and the resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/30) to give ethyl 10-[(3R,4R)-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochroman-4-yl]-2-(4,4,5,5,5-pentafluoropentyl)-8-decenoate (3.46 g, Yield 72%) as an oil. under reflux for 6 hours the solvent was distilled off the resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/30)

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 446 mg of triphenylphosphine is dissolved in 2 cm3 of methylene chloride, cooled down to 10° C., 116 mg of imidazole is added, agitation is carried out for 15 minutes, 431 mg of iodine is added, agitation is carried out for 30 minutes, 0.21 cm3 of 4,4,5,5,5-pentafluoro 2-penten 1-ol is added, agitation is carried out for 4 hours at ambient temperature, the organic phase is washed with a saturated aqueous solution of sodium thiosulphate and a chloromethylenic solution of 4,4,5,5,5-pentafluoro iodopentane is obtained which is used as it is in the continuation of the synthesis. The operation is carried out as indicated in Example 8 Stage F, starting with 618 mg of the thioacetate prepared below in 7 cm3 of methanol and the chloromethylenic solution of the iodated derivative prepared above. 1.2 g of expected product is obtained. agitation is carried out for 30 minutes agitation is carried out for 4 hours at ambient temperature the organic phase is washed with a saturated aqueous solution of sodium thiosulphate

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

Procedure: Starting with the (3S,4S)-7-methoxy-3-(4-methoxy-phenyl)-3-methyl-4-(2-propenyl)thiochroman prepared in Example 3 and ethyl 2-(4,4,5,5,5-pentafluoropentyl)-9-decenoate separately prepared from 1-iodo-4,4,5,5,5-pentafluoropentane, diethyl malonate and 1-iodo-7-octene, a procedure analogous to that as shown in Example 2 or 3 was repeated to give 11-[(3S,4S)-7-hydroxy-3-(4-hydroxyphenyl)-3-methylthiochroman-4-yl]-2-(4,4,5,5,5-pentafluoropentyl)undecanoic acid.

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

Procedure: Starting with the (3S,4S)-7-methoxy-3-(4-methoxy-phenyl)-3-methyl-4-(2-propenyl)thiochroman prepared in Example 3 and ethyl 2-(4,4,5,5,5-pentafluoropentyl)-9-decenoate separately prepared from 1-iodo-4,4,5,5,5-pentafluoropentane, diethyl malonate and 1-iodo-7-octene, a procedure analogous to that as shown in Example 2 or 3 was repeated to give 11-[(3S,4S)-7-hydroxy-3-(4-hydroxyphenyl)-3-methylthiochroman-4-yl]-2-(4,4,5,5,5-pentafluoropentyl)undecanoic acid.

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

Procedure: Starting with the (3R,4R)-7-methoxy-3-(4-methoxy-phenyl)-3-methyl-4-(2-propenyl)thiochroman prepared in Example 2 and ethyl 2-(4,4,5,5,5-pentafluoropentyl)-9-decenoate separately prepared from 1-iodo-4,4,5,5,5-pentafluoropentane, diethyl malonate and 1-iodo-7-octene, a procedure analogous to that as shown in Example 2 or 3 was repeated to give 11-[(3R,4R)-7-hydroxy-3-(4-hydroxyphenyl)-3-methylthiochroman-4-yl]-2-(4,4,5,5,5-pentafluoropentyl)undecanoic acid.

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

Procedure: Starting with the (3R,4R)-7-methoxy-3-(4-methoxy-phenyl)-3-methyl-4-(2-propenyl)thiochroman prepared in Example 2 and ethyl 2-(4,4,5,5,5-pentafluoropentyl)-9-decenoate separately prepared from 1-iodo-4,4,5,5,5-pentafluoropentane, diethyl malonate and 1-iodo-7-octene, a procedure analogous to that as shown in Example 2 or 3 was repeated to give 11-[(3R,4R)-7-hydroxy-3-(4-hydroxyphenyl)-3-methylthiochroman-4-yl]-2-(4,4,5,5,5-pentafluoropentyl)undecanoic acid.

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

Procedure: Ethyl 2-(4,4,5,5,5-pentafluoropentyl)-8-nonenoate was separately prepared from 1-iodo-4,4,5,5,5-pentafluoropentane, diethyl malonate and 1-iodo-6-heptene. A solution of this compound (4.55 g, 13.21 mmol), (3R,4R)-7-methoxy-3-(4-methoxyphenyl)-3-methyl-4-(2-propenyl)thiochroman (2.5 g, 7.342 mmol) and benzylidene-bis(tricyclohexylphosphine)dichlororuthenium (302 mg, 0.367 mmol) in dichloromethane (60 ml) was heated under reflux for 6 hours. After the reaction was completed, the solvent was distilled off and the resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/30) to give ethyl 10-[(3R,4R)-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochroman-4-yl]-2-(4,4,5,5,5-pentafluoropentyl)-8-decenoate (3.46 g, Yield 72%) as an oil. under reflux for 6 hours the solvent was distilled off the resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/30)

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

Procedure: Ethyl 2-(4,4,5,5,5-pentafluoropentyl)-8-nonenoate was separately prepared from 1-iodo-4,4,5,5,5-pentafluoropentane, diethyl malonate and 1-iodo-6-heptene. A solution of this compound (4.55 g, 13.21 mmol), (3R,4R)-7-methoxy-3-(4-methoxyphenyl)-3-methyl-4-(2-propenyl)thiochroman (2.5 g, 7.342 mmol) and benzylidene-bis(tricyclohexylphosphine)dichlororuthenium (302 mg, 0.367 mmol) in dichloromethane (60 ml) was heated under reflux for 6 hours. After the reaction was completed, the solvent was distilled off and the resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/30) to give ethyl 10-[(3R,4R)-7-methoxy-3-(4-methoxyphenyl)-3-methylthiochroman-4-yl]-2-(4,4,5,5,5-pentafluoropentyl)-8-decenoate (3.46 g, Yield 72%) as an oil. under reflux for 6 hours the solvent was distilled off the resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/30)