4-(4-Trifluoromethylphenyl)benzylchloride → HCID 10288480, compound

Participants

Reaction Steps

Preparation of Indan-4-ol (compound 12A) A mixture of 4-hydroxy-indan-1-one (5.0 g, 33.7 mmol), sodium cyanoborohydride (6.4 g, 101.1 mmol), and zinc iodide (32.3 g, 101.1 mmol) in dichloromethane, was heated at reflux for two hours. The reaction mixture was then filtered through 50 g SiO2 while still warm, eluting further with dichloroethane. The filtrate was collected and concentrated under vacuum. The residue was added to diethyl ether and the resulting white precipitate was filtered off. The filtrate was collected and concentrated in vacuo to give 4.2 g of the title, compound with purity high enough for subsequent use. 400 MHz 1H NMR (DMSO-d6) δ 9.06 (s, 1H), 6.86 (t, 1H, J=7.8 Hz), 6.59 (d, 1H, J=7.8 Hz), 6.48 (d, 1H, J=7.8 Hz), 2.75 (t, 2H, J=7.3 Hz), 2.67 (t, 2H, J=7.3 Hz), 1.92 (m, 2H). Step 2. Preparation of 7-Thiocyanato-indan-4-ol (compound 12B) The title compound was prepared in the manner analogous to Example 1B using 12A. MS m/z 192 (M+1). Step 3. Preparation of (7-Mercapto-indan-4-yloxy)-acetic acid methyl ester (compound 12C) 7-Thiocyanato-indan-4ol (Example 12B) (1.47 g, 7.7 mmol), cesium carbonate (3.77 g, 11.6 mmol) and methyl bromoacetate (1.24 g, 8.08 mmol) were stirred in 20 ml acetonitrile at ambient temperature for 4 h. The reaction was filtered and concentrated. The crude product was treated under the conditions of Example 1D to afford the title product. MS m/z 239 (M+1). Step 4. Preparation of [7-(4′-Trifluoromethyl-biphenyl-4-ylmethylsulfanyl)-indan-4-yloxy]-acetic acid methyl ester (compound 12D) The title compound was prepared in the manner analogous to Example 1F using 12C and 3B. MS m/z 473 (M+1). Step 5. Preparation 17-(4′-Trifluoromethyl-biphenyl-4-ylmethylsulfanyl)-indan-4-yloxy]-acetic acid (compound 12) The title compound was prepared in the manner analogous to Example 1 using 12D. mp 158-159° C.; 400 MHz 1H NMR (DMSO-d6) δ 12.94 (br(s), 1H), 7.82 (d, 2H, J=8 Hz), 7.74 (d, 2H, J=8.8 Hz), 7.60 (d, 2H, J=6.4 Hz), 7.31 (d, 2H, J=8 Hz), 7.08 (d, 1H, J=8.8 Hz), 6.58 (d, 1H, J=8.4 Hz), 4.61 (s, 2H), 4.06 (s, 2H), 2.72 (m, 4H), 1.90 (q, 2H); MS m/z 457 (M−1).

Provenance & Evidence