1-(4-bromophenyl)propan-2-one

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: The title compound was prepared according to the procedure of step 1 in the Example 190 using (4-bromophenyl)acetone and 4-methylthiobenzaldehyde, instead of phenylacetone and 4-bromobenzaldehyde.

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

Procedure: 7-Bromo-3-methylnaphthalen-1-ol was prepared in a similar manner as 6-chloro-3-methylnaphthalen-1-ol in Example 5 except using 1-(4-bromophenyl)propan-2-one instead of 1-(3-chlorophenyl)propan-2-one. To a solution of 7-bromo-3-methylnaphthalen-1-ol (11.5 g, 48.5 mmol) in dichloromethane (145 mL) at 0° C. was added a 1 M titanium(IV) chloride solution in dichloromethane (48.5 mL, 48.5 mmol) and stirred for 20 min. Ethyl glyoxylate (50% solution in PhCH3, 10.6 mL, 53.3 mmol) was added over 15 minutes and stirred for 1 hour at 0° C. The reaction was quenched by the addition of Rochelle's salt solution and stirred at room temperature for 14 hours. The layers were separated, and the aqueous layer was extracted with CH2Cl2. The combined organic layers were dried, filtered, concentrated and purified by flash column chromatography (EtOAc/Hexanes) to provide the desired product. 1H-NMR: 400 MHz, (CDCl3) δ: 8.52 (s, 1H), 8.34 (s, 1H), 7.49 (m, 2H), 7.13 (s, 1H), 5.67 (s, 1H), 4.24 (m, 1H), 4.16 (m, 1H), 2.29 (s, 3H), 1.23 (m, 3H). stirred for 1 hour at 0° C The reaction was quenched by the addition of Rochelle's salt solution stirred at room temperature for 14 hours The layers were separated the aqueous layer was extracted with CH2Cl2 The combined organic layers were dried filtered concentrated purified by flash column chromatography (EtOAc/Hexanes)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 4-bromophenylacetone (5.0 g, 23.5 mmol, 1.0 equiv) (Acros Organics 34216) was added N,N-dimethylformamide dimethyl acetal (11.3 ml, 84.6 mmol, 3.6 equiv) and the mixture was heated to 90° C. for 6 hours. The solvents were removed and the resulting gum was dissolved in ethanol (235 ml) with additional heating. Hydrazine hydrate (1.37 ml, 28.2 mmol, 1.2 equiv) was added and the mixture was heated to reflux for 15 hours. The solvents were removed under reduced pressure and the solid was triturated with dichloromethane to afford the title compound, 2.24 g (40%); LCMS (PS-A) Rt 2.87 min [M+H]+ 238. Further material could be isolated from the mother liquor. The solvents were removed the resulting gum was dissolved in ethanol (235 ml) with additional heating the mixture was heated to reflux for 15 hours The solvents were removed under reduced pressure the solid was triturated with dichloromethane

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

Procedure: To a solution of 4-bromophenylacetone (5.00 g, 23.5 mmol) in ethanol (100 mL) at 0° C., was added sodium borohydride (976 mg, 25.8 mmol) portionwise over 5 min. The mixture was stirred at rt for 15 h, then quenched with 5% citric acid. The volatile solvent was removed in vacuo. The mixture was diluted with water, the pH was adjusted to 4.5 with 1N HCl, then aqueous phase was extracted with CH2Cl2 (3×). The combined organic washed with brine, dried (Na2SO4), filtered through a pad of SiO2 (eluted with 10% EtOAc/CH2Cl2) and concentrated to afford 4.90 g of 77A as a colorless oil. MS (ESI) m/z 197.1 (M-OH)+. quenched with 5% citric acid The volatile solvent was removed in vacuo The mixture was diluted with water aqueous phase was extracted with CH2Cl2 (3×) The combined organic washed with brine dried (Na2SO4) filtered through a pad of SiO2 (eluted with 10% EtOAc/CH2Cl2) concentrated

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

Procedure: The title compound (54 mg, colorless oil) was prepared from 1-(4-bromophenyl)propan-2-one (130 mg) and 3-oxa-8-azabicyclo[3.2.1]octane (100 mg), as in Reference Example P-R5-1.

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

Procedure: The title compound (54 mg, colorless oil) was prepared from 1-(4-bromophenyl)propan-2-one (130 mg) and 3-oxa-8-azabicyclo[3.2.1]octane (100 mg), as in Reference Example P-R5-1.

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

Procedure: 1-(4-Bromophenyl)propan-2-one (2.03 g) was dissolved in CHCl3 (40 mL), and morpholine (1.24 mL) was added thereto, followed by stirring at room temperature overnight and then at 60° C. for 4 hours. NaBH(OAc)3 (4.03 g) and acetic acid (1.1 mL) were sequentially added thereto, followed by stirring overnight. The reaction was terminated by addition of water, and the reaction solution was separated between CHCl3 and a saturated aqueous NaHCO3 solution. The residue was purified by silica gel column chromatography (mobile phase: CHCl3/EtOAc=80/20 to 60/40 (v/v)) to yield the title compound (1.67 g, colorless oil). at 60° C. for 4 hours by stirring overnight The reaction was terminated by addition of water the reaction solution was separated between CHCl3 The residue was purified by silica gel column chromatography (mobile phase: CHCl3/EtOAc=80/20 to 60/40 (v/v))

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A flask containing the crude ethyl 4-(4-bromophenyl)-3-methylbut-2-enoate from above (˜30 grams) was treated with concentrated H2SO4 (120 mL) and warmed to 50° C. for 2.5 h. The reaction was poured onto ˜500 mL of crushed ice. Once the ice had thawed, the brown suspension was extracted with two portions of EtOAc (500 mL and 100 mL, respectively). The two extracts were combined, washed with saturated NaHCO3, dried (MgSO4), filtered, and concentrated to ˜55 mL. The residue was treated with DCM and wet-loaded onto a silica gel column and purified by flash chromatography (ethyl acetate/hexanes) giving the desired product (16.6 g, 60% yield over 2 steps from 1-(4-bromophenyl)propan-2-one. 1H NMR (400 MHz, CDCl3) δ 8.29 (d, J=1.9 Hz, 1H), 7.57 (d, J=8.6 Hz, 1H), 7.50 (dd, J=8.6, 2.0 Hz, 1H), 7.17 (s, 1H), 6.67 (s, 1H), 2.42 (s, 3H). the brown suspension was extracted with two portions of EtOAc (500 mL and 100 mL washed with saturated NaHCO3 dried (MgSO4) filtered concentrated to ˜55 mL The residue was treated with DCM and wet-loaded onto a silica gel column purified by flash chromatography (ethyl acetate/hexanes)

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

Procedure: The title compound was prepared according to the procedure of step 1 in the Example 190 using (4-bromophenyl)acetone and 4-methylthiobenzaldehyde; instead of phenylacetone and 4-bromobenzaldehyde.

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

Procedure: The title compound was prepared according to the procedure of step 1 in the Example 190 using (4-bromophenyl)acetone and 4-methylthiobenzaldehyde; instead of phenylacetone and 4-bromobenzaldehyde.