4-bromo-2-methylphenol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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: Synthesised by analogous methods to Intermediate 2b, using 4-bromo-2-methyl-phenol at Stage 6 of Scheme 2. m/z 504 [M+H]+.

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

Procedure: Using essentially the same procedure as Example 5-20, Step 1, 4-bromo-2-methylphenol (1.00 g, 5.35 mmol), cesium carbonate (3.48 g, 10.7 mmol) and 4-bromo-2-methyl-2-butene (0.75 mL, 6.42 mmol) afforded the desired product as a pale-yellow oil.

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

Procedure: An ice-cold solution of 4-bromo-2-methylphenol (5.6 g, 30 mmol) and pyridine (6.1 mL, 75 mmol) in 50 mL of anhydrous dichloromethane was treated with a solution of acetyl chloride (2.8 mL, 26 mmol) in 5 mL of anhydrous dichloromethane. After 2 hours, the reaction mixture was concentrated in vacuo. The resulting residue was treated with crushed ice, diluted with 150 mL of dichloromethane, washed with water, dried over sodium sulfate, filtered, and concentrated in vacuo to give 6.9 g of 4-bromo-2-methylphenyl acetate as a light brown oil (quantitative yield). the reaction mixture was concentrated in vacuo The resulting residue was treated with crushed ice diluted with 150 mL of dichloromethane washed with water dried over sodium sulfate filtered concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of DIAD (0.44 mL, 2.40 mmol) in THF (1.0 mL) was added dropwise to an ice-cold solution of 11-ethyl-5,11-dihydro-8-(2-hydroxyethyl)-5-methyl-6H-dipyrido[3,2-b:2′,3′-e][1,4]diazepin-6-one (480 mg, 1.61 mmol), 4-bromo-2-methylphenol (318 mg, 1.70 mmol) and PPh3 (629 mg, 2.40 mmol) in THF (20 mL) at 25° C. The mixture was stirred at 0° C. for 3 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by flash chromatography (Hexane:EtOAc, 7:3) to yield the title compound (437 mg, 58% yield) as a white solid. The reaction mixture was concentrated under reduced pressure the residue was purified by flash chromatography (Hexane:EtOAc, 7:3)

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

Procedure: Pd(PPh3)4 (69.3 mg, 0.06 mmol) was added to a degassed (N2 for 15 min) solution of 4-bromo-2-methylphenol (225 mg, 1.20 mmol), 2-formylfuran-5-boronic acid (177 mg, 1.26 mmol) and aqueous 0.4 M Na2CO3 (6 mL) in MeCN (12 mL). The mixture was heated to reflux for 12 h. The hot mixture was filtered and the cake was washed with MeCN (6 mL). The filtrate was concentrated to half the volume and was diluted with EtOAc. The resulting solution was washed with water and brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (Hexane:EtOAc, 7:3) to provide the title compound (115 mg, 47% yield) as a yellow solid. The mixture was heated to reflux for 12 h The hot mixture was filtered the cake was washed with MeCN (6 mL) The filtrate was concentrated to half the volume was diluted with EtOAc The resulting solution was washed with water and brine dried (MgSO4) filtered concentrated under reduced pressure The residue was purified by flash chromatography (Hexane:EtOAc, 7:3)

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

Procedure: 4-Bromo-2-methyl-phenol (3.63 g, 19.41 mmol) was dissolved in dichloromethane (18 mL) and triethylamine (5.41 mL, 38.80 mmol), cooled to 0° C., then treated with methyl chloroformate (2.25 mL, 29.12 mmol) and allowed to warm to room temperature over 2 h. The reaction was quenched with water and the layers separated. The aqueous layer was extracted with dichloromethane and the combined organic extracts was dried over Na2SO4, filtered, and concentrated in vacuo to yield an oil that was purified by silica gel chromatography (10% ethyl acetate/hexane) to yield 4-bromo-2-methylphenyl methyl carbonate (4.1 g, 86% yield) as a white solid. 1H NMR (400.0 MHz, DMSO-d6) δ 7.56 (d, J=2.1 Hz, 1H), 7.44 (dd, J=2.3, 8.6 Hz, 1H), 7.18 (d, J=8.6 Hz, 1H), 3.84 (s, 3H), 2.15 (s, 3H). The reaction was quenched with water the layers separated The aqueous layer was extracted with dichloromethane the combined organic extracts was dried over Na2SO4 filtered concentrated in vacuo to yield an oil that was purified by silica gel chromatography (10% ethyl acetate/hexane)

Conditions: temp:0.00; pressure:0.00; stir: