| 51% |
With sodium hydroxide In water at 140℃; for 1.5h; |
13 Step a) cyclopropyl(4-hydroxyphenyl)methanone (Ph13)
p-Hydroxy-y-chlorobutyrophenone (4.95 g) was added in portions during approximately 30 mm to a solution of NaOH (8 mL, aq, 50% w/w), then NaOH (35 mL, aq, 25% w/w) was addedfollowed by p-hydroxy y-chlorobutyrophenone (4.95 g) in one portion. The temperature was lowered to i40 °C and NaOH (8 g) was added. After 90 mi H20 (i0 ml) was added, and after additional 60 mm, the reaction mixture was cooled, diluted with H20 and neutralized with HOAc ( 27-30m1) to pH 7 The formed precipitate was filtered, washed with H20 and dried in vacuum. The solids were triturated in CHCI3 (200 ml) at 40°C during i 0 mm, then at RTovernight. The slurry was heated to 40 °C during 30 mm, then filtered. The filtrate was dried (MgSO4), filtered and concentrated to 7Oml. Hexane was added and an oil was formed that eventually became crystals. The slurry was filtered, solids washed with CHCI3/hexane and dried, which gave the title compound (4.i5 g, 5i%). |
| 51% |
With sodium hydroxide In water at 140℃; for 3h; |
13.a cyclopropyl(4-hydroxyphenyl) methanone (Ph 13)
p-Hydroxy-y-chlorobutyrophenone (4.95 g) was added in portions during approximately 30 mm to a solution of NaOH (8 mL, aq, 50% wlw), then NaOH (35 mL, aq, 25% w/w) was addedfollowed by p-hydroxy y-chlorobutyrophenone (4.95 g) in one portion. The temperature was lowered to 140 °C and NaOH (8 g) was added. After 90 mm, H20 (10 ml) was added, and after additional 60 mm, the reaction mixture was cooled, diluted with H20 and neutralized with HOAc ( 27-30m1) to pH 7 The formed precipitate was filtered, washed with H20 and dried in vacuum. The solids were triturated in CHCI3 (200 ml) at 40°C during 10 mm, then at RT overnight. The slurry was heated to 40 °C during 30 mm, then filtered. The filtrate was dried(MgSO), filtered and concentrated to 70ml. Hexane was added and an oil was formed that eventually became crystals. The slurry was filtered, solids washed with CHCI3/hexane and dried, which gave the title compound (4.15 g, 51%). |
| 51% |
With sodium hydroxide In water at 140℃; for 2.5h; |
a Step a) cvclopropyl(4-hvdroxyphenyl)methanone (Ph13)
p-Hydroxy-v-chlorobutyrophenone (4.95 g) was added in portions during approximately 30 min to a solution of NaOH (8 mL, aq, 50% w/w), then NaOH (35 mL, aq, 25% w/w) was added followed by p-hydroxy γ-chlorobutyrophenone (4.95 g) in one portion. The temperature was lowered to 140 °C and NaOH (8 g) was added. After 90 min, H20 (10 mL) was added, and after additional 60 min, the reaction mixture was cooled, diluted with H20 and neutralized with HOAc ( ~ 27-30ml) to pH =7 The formed precipitate was filtered, washed with H20 and dried in vacuum. The solids were triturated in CHCI3 (200 ml) at 40°C during 10 min, then at RT overnight. The slurry was heated to 40 °C during 30 min, then filtered. The filtrate was dried (MgS04), filtered and concentrated to =70ml. Hexane was added and an oil was formed that eventually became crystals. The slurry was filtered, solids washed with CHCI3/hexane and dried, which gave the title compound (4.15 g, 51 %). |
| 51% |
With sodium hydroxide In water at 140℃; for 2.5h; |
a Step a) Cyclopropyl (4-hydroxyphenyl) methanone (Ph13)
NaOH solution (8 mL, aqueous solution, 50% w / w) in about 30 minP-hydroxy-γ-chlorophenone (4.95 g) was added in portions, followed by NaOH (35 mL,Aqueous solution, 25% w / w), followed by p-hydroxyγ-chlorophenone (4.95 g). The temperature was reduced to 140 ° C and NaOH (8 g) was added. After 90 minutes,H2O (10 ml) was added and after an additional 60 min, the reaction mixture was cooled,Dilute with H2O and neutralize with HOAc (≈ 27-30 ml) to pH ≈7. The precipitate formed was filtered, washed with H2O and dried in vacuo.The solid was triturated in CHCl3 (200 ml) over 10 min at 40 ° C,Then overnight at RT. Heating the slurry to 40 ° C during 30 min,Then filtered. The filtrate was dried (MgSO4),Filter and concentrate to ≈70 ml. Hexane was added and an oil was formed, which eventually became crystals. The slurry was filtered, the solid was washed with CHCl3 / hexane and dried, which gave the title compound (4.15 g, 51%). |
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With sodium hydroxide |
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With sodium hydroxide Heating; |
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Stage #1: γ-chloro-4-hydroxybutyrophenone With potassium <i>tert</i>-butylate In tetrahydrofuran at -5 - 0℃; for 1h;
Stage #2: With phosphoric acid In tetrahydrofuran at 20℃; for 2h; |
Cyclopropyl-(4-hydroxy-phenyl)-methanone
A mixture of t-BuOK (30 g) and dry THF (60 mL) was cooled to -5° C. A solution of 4-chloro-1-(4-hydroxy-phenyl)-butan-1-one (24 g) in dry THF (80 mL) was added at -5 to 0° C. The mixture was stirred at 0° C. for one hour and added to a stirred solution of phosphoric acid (85%, 18.1 g) in water (100 mL), then warmed slowly to room temperature and stirred for 2 h. The mixture was extracted with EA (100 mL*2), the combined organic phase was washed with brine (50 mL). The combined aqueous layers were re-extracted with EA (80 mL). The combined organic layers were concentrated, and the residue was purified by SGC (PE:EA=4:1) to provide cyclopropyl-(4-hydroxy-phenyl)-methanone. MS ESI+: m/z=163 [M+H]+. |
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