Reacción #712875

Ecuación de reacción

(1S,2S)-2-{4-[(R)-7-Fluoro-4-(3-fluoro-4-hydroxy-phenoxy)-indan-1-yloxy]-phenyl}-cyclopropanecarboxylic acid ethyl ester

di-tert-butyl azodicarboxylate

3-methylthiopropanol

triphenylphosphine

3-methylthiopropanol

di-tert-butyl azodicarboxylate

oxone

Intermediate 9

(1S,2S)-2-{4-[(R)-7-Fluoro-4-(3-fluoro-4-hydroxy-phenoxy)-indan-1-yloxy]-phenyl}-cyclopropanecarboxylic acid ethyl ester

→

title compound

(1S,2S)-2-(4-{(R)-7-Fluoro-4-[3-fluoro-4-(3-methanesulfonyl-propoxy)-phenoxy]-indan-1-yloxy}-phenyl)-cyclopropanecarboxylic acid ethyl ester

Disolventes

ethyl acetate

tetrahydrofuran

water

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGthe mixture stirred for a further 24 hours
2. 2
   OtroThe solvent is removed under vacuum
3. 3
   Otrothe residue is purified by flash chromatography (gradient of ethyl acetate in cyclohexane)
4. 4
   Otroto give a residue which
5. 5
   workup.ADDITIONis added (380 mg, 0.62 mmol)
6. 6
   workup.STIRRINGThe mixture is stirred for 2 hours
7. 7
   Lavadowashed with water
8. 8
   OtroThe solvent is removed
9. 9
   Otrothe residue is purified by flash chromatography (0-50% ethyl acetate in cyclohexane)

Procedimiento

(1S,2S)-2-{4-[(R)-7-Fluoro-4-(3-fluoro-4-hydroxy-phenoxy)-indan-1-yloxy]-phenyl}-cyclopropanecarboxylic acid ethyl ester (Intermediate 9, 200 mg, 0.43 mmol), 3-methylthiopropanol (0.044 mL, 0.43 mmol), triphenylphosphine (120 mg, 0.47 mmol) and di-tert-butyl azodicarboxylate (110 mg, 0.47 mmol) are suspended in dry tetrahydrofuran (5 mL) and stirred overnight. A further quantity of 3-methylthiopropanol (0.044 mL, 0.43 mmol), and di-tert-butyl azodicarboxylate (110 mg, 0.47 mmol) are added and the mixture stirred for a further 24 hours. The solvent is removed under vacuum and the residue is purified by flash chromatography (gradient of ethyl acetate in cyclohexane) to give a residue which is suspended in a 1:1 mixture of tetrahydrofuran and water (4 mL) and oxone is added (380 mg, 0.62 mmol). The mixture is stirred for 2 hours then diluted with ethyl acetate and washed with water. The solvent is removed and the residue is purified by flash chromatography (0-50% ethyl acetate in cyclohexane) to give the title compound. (Yield 50 mg). LC (METHOD 5): tR=1.47 min; Mass spectrum (ES+): m/z=587 [M+H]+.

Fuente