2-Bromo-1-cyclopropylethanone

A solution of cyclopropyl methyl ketone (20.7 mL, 220 mmol) in MeOH (100 mL) was treated with bromine (11.3 mL, 220 mmol) at -5° C. for 2 hours. 50 mL water was added and the reaction was warmed up to room temperature overnight. The mixture was diluted with water (150 mL) and extracted with ethyl ether. The organic phases were separated and washed with NaHCOExample 21 : (2R, 75R)-2-[(l-Aminoisoquinolin-6-yl)amino]-7-[(25)-2-cyclopropyl-2- hydroxyethoxy]-8-fluoro-4, 15, 20-trimethyl-13-oxa-4, l l- diazatricyclo[14.2.2.16, 10]henicosa-l(18), 6, 8, 10(21), 16, 19-hexaene-3, 12-dione; trifluoroacetic acid -Bromo- 1 -cyclopropylethanone [00300] To a solution of 1 -cyclopropylethanone (18.85 mL, 201 mmol) in MeOH (120 mL) at 0 °C was added bromine (10.40 mL, 202 mmol) dropwise. The reaction mixture was stirred at 0 °C for 1 h, rt for 30 min, and quenched by addition of water. The mixture was extracted with ether (3x100 mL). The organic layer was washed with sat. sodium bicarbonate and brine, dried over MgS0To a cooled (ice-water bath) solution of 1 -cyclopropylethanone (4.20 g, 50.0 mmol) in methanol (35 mL) was added dropwise bromine (7.99 g, 2.58 mL, 50 mmoL). The mixture was stirred at 0Step 1. To a solution of cyclopropyl methyl ketone (10.0 g, 0.12 mol) in methanol (80 mL) was added bromine (19.0 g, 0.12 mol) dropwise at 0 °C. The resulting mixture was allowed to cool below 10 °C for 30 minutes, followed by continued stirring at room temperature for 30 minutes. The reaction was quenched with water (150 mL) and extracted with ethyl ether (3 x 150 mL). The extract was sequentially washed with NaReference Example 256: 2-Bromo-l-cyclopropyI-ethanone. Bromine (6.2 mL, 119 mmol) was added slowly to a solution of 1-cyclopropyl- ethanone (10.0 g, 119 mmol) in methanol (50 mL) at 0 °C. The reaction mixture was warmed to 10 °C and stirred for 45 min, during which time the colour was discharged. The mixture was diluted with water (50 mL) and stirred overnight. The mixture was further diluted with water (200 mL) and whole extracted with ether. The organic phase was washed successively with 10percent sodium carbonate solution, water and brine, dried over anhydrous calcium chloride and concentrated to afford 2-bromo-l-cyclopropyl- ethanone (17.0 g, 88 percent).To a stirred solution of 1-cyclopropylethanone (50 g, 595 mmol) in MeOH (350 mL) at 0 °C (ice bath) was added bromine (32 mL, 595 mmol) dropwise over a period of 1hour (the initial red colour of the reaction mixture became colourless by the end of the addition of bromine). The resulting solution was then stirred below 5 °C for 4 hours, then water (175 mL) was added and the reaction mixture stirred at room temperature for 16 hours. The reaction mixture was then poured into water (1000 mL) and extracted with CH2C12 (2 x 1000 mL). The combined organic layers was washed withsaturated aqueous NaHCO3 solution (500 mL), water (500 mL) and finally with brine (500 mL). The organic layer was dried over Na2504, filtered and concentrated in vacuo to give a light-brown oil. Pure 2-bromo-l-cyclopropyl-ethanone was obtained by vacuum distillation of this crude oil at 100 °C (59 g, 6 1percent).‘H NMR (400 MHz, CDCI3) 6 = 4.01 (s, 2H), 2.22-2.17 (m, 1H), 1.14-1.11 (m, 2H), 1.03-0.99 (m, 2H).To a stirred solution of 1-cyclopropylethanone (50 g, 595 mmol) in MeOH (350 mL) at 0 °C (ice bath)was added bromine (32 mL, 595 mmol) dropwise over a period of 1 hour (the initial red colour of thereaction mixture became colourless by the end of the addition of bromine). The resulting solution was then stirred below 5 °C for 4 hours, then water (175 mL) was added and the reaction mixture stirred at room temperature for 16 hours. The reaction mixture was then poured into water (1000 mL) and extracted with CH2CI2 (2 x 1000 mL). The combined organic layers was washed with saturated aqueousNaHCO3 solution (500 mL), water (500 mL) and finally with brine (500 mL). The organic layer was dried over Na2504, filtered and concentrated in vacuo to give a light-brown oil. Pure 2-bromo-1-cyclopropyl- ethanone was obtained by vacuum distillation of this crude oil at 100 °C (59 g, 61percent).1H NMR (400 MHz, CDCI3) ö = 4.01 (s, 2H), 2.22-2.17 (m, 1 H), 1.14-1.11 (m, 2H), 1.03-0.99 (m, 2H).Step A: To a stirred ice-cooled solution of cyclopropyl methyl ketone (21 g, 1 eq.) in methanol (150 mL) was added dropwise bromine (12.9 ml, 1 eq.). The reaction was allowed to proceed(decolorization) below 10 PREPARATION N-rri -(4-cvclopropylthiazol-2-yl)cvclopropyllmethyll-2- (trifluoromethyl)benzamide (Compound A10)Step 1 : 2-bromo-1 -cvclopropyl-ethanone 1-Cyclopropylethanone (20 g, 237.8 mmol) was dissolved in Methanol (1 18.9 mL). At 0°C was Bromine (38.00 g, 237.8 mmol) added drop wise in 30 minutes. The brown solution was stirred at 0°C. After 5 minutes the reaction mixture was exothermic and the temperature raised to 32°C. Afterwards the solution was colorless. The reaction mixture was stirred for 30 minutes. Then 250ml water were added carefully. The emulsion was extracted 3 times with 100ml Diethyl ether. The combined organic phases were washed with 70ml 10percent IS^COg, 75ml water and 75ml brine. The organic phase was dried withNa2SC>4 , filtrated and evaporated at 300mbar/40°C. The desired product was obtained as a brownish liquid (41.4g).To a stirred solution of 18 cyclopropyl methyl ketone (25 g, 297.6 mmol) in 19 methanol (125 mL) was added 20 bromine (47.5 g, 297.2 mmol) drop wise at 0° C. under inert atmosphere and stirred at same temperature for 2 h. To this, 21 water (125 mL) was added and stirred at room temperature for 16 h. After completion of reaction (monitored by TLC; 0.4 Rf, 10percent 13 EtOAc in 14 petroleum ether), the reaction mixture was diluted with water (75 mL) and extracted with diethyl ether (2×250 mL). The combined organic layer was washed with saturated NaHCO[0302] A solution of cyclopropyl methyl ketone (20.7 mL, 220 mmol) in MeOH (100 mL) was treated with bromine (11.3 mL, 220 mmol) at -5°C for 2 h. 50 mL of water was added and the reaction was warmed up to room temperature overnight. The mixture was diluted with water (150 mL) and extracted with ethyl ether. The organic phases were separated and washed with NaHC03, dried (Na2S04), and concentrated to dryness, affording light yellow oil (35 g).To a methanol solution (12.0 mL) of cyclopropyl methyl ketone (1.80 g) was added under ice-cooling bromine (1.10 mL), and the reaction mixture was stirred at the same temperature for 10 min.

Molecular Weight:163.01
XLogP3:1.2
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:2
Exact Mass:161.96803
Monoisotopic Mass:161.96803
Topological Polar Surface Area:17.1
Heavy Atom Count:7
Complexity:86.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes