4-bromobut-1-ene

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: 1-bromo-3-butene (39.0 mmol) and triethyl phosphite (1 g, 6 mmol) were dissolved and reacted in CHCl3 (30 mL). Then, the reaction solution was refluxed for 12 hours, cooled to room temperature and filtered through a glass filter. Chloroform (CHCl3) was completely removed from the solution under vacuum to thereby give an oily compound as the title compound. The 1H NMR results of the compound thus obtained are given as follows. Then, the reaction solution was refluxed for 12 hours filtered through a glass filter Chloroform (CHCl3) was completely removed from the solution under vacuum

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

Procedure: Magnesium (4.2 g, 173 mmol) was activated by washing with dilute HCl, water and acetone and was then dried in vacuo. ZnBr2 (37 g, 165 mmol) was sublimed under reduced pressure (approx. 5-20 mmHg) by gentle heating in a glovebox. The glovebox was used as it was extremely humid in the lab. Mg and ZnBr2 were mixed in a dry 3-necked flask under N2 and dry THF (30 mL) was added. 4-Bromo-1-butene (25.1 g, 186 mmol) dissolved in dry THF (175 mL) was added dropwise to the Mg/ZnBr2 slurry and, during the addition, the reaction mixture turned greyish and then black. Some heat was also evolved (>40° C.). After complete addition, the mixture was heated to 50° C. overnight. 4-Bromobenzonitrile (30.5 g, 167 mmol) was co-evaporated with toluene twice and was then dissolved in dry THF (250 ml) together with Pd(PPh3)4 (5 g, 4.3 mmol, 2.5 mole). The slurry was added to the Grignard reagent and the reaction mixture was stirred at room temperature overnight. HCl (500 mL, 3 M) was added dropwise to the reaction mixture, and the resulting solution was extracted with ether (1000+3×500 mL), the combined ether solutions were washed with NaHCO3 (satd. 3×250 mL), dried, filtered and evaporated. The crude product (29.7 g) was subjected to Dry-Flash chromatography (diameter 12 cm, height 5 cm, heptane:EtOAc (99:1 to 90:10)) to give 21.2 g of the sub-title compound contaminated with 4-bromobenzonitrile (about 20%). This material was used in the next step. by washing with dilute HCl, water and acetone was then dried in vacuo by gentle heating in a glovebox (>40° C.) After complete addition the resulting solution was extracted with ether (1000+3×500 mL) the combined ether solutions were washed with NaHCO3 (satd. 3×250 mL) dried filtered evaporated

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of (7S,10S)-7-isopropyl-4,4-dimethyl-10-vinyl-9-oxa-16-thia-3,6,13,18-tetraazabicyclo[13.2.1]octadeca-1(17),15(18)-diene-2,5,8,12-tetraone (20 mg, 0.047 mmole) in 2 mL 1,2-dichloroethane was added 4-bromo-1-butene (25.6 mg, 0.19 mmole) and Zhan-1 catalyst (3.2 mg, 0.0047 mmole). The mixture was briefly degassed and then heated in a sealed tube at 85° C. overnight. The crude product was concentrated and passed through a silica gel plug to get a mixture of the desired product and recovered starting material (2:1 ratio). It was further purified by reversed phase chromatography, eluted with 0-80% water/CH3CN to get the desired product (8 mg, 32% yield). The mixture was briefly degassed The crude product was concentrated to get

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

Procedure: Crushed KOH (0.0484 g, 0.862 mmol, 1.2 equiv) was added to 2-nitro-N-phenylbenzenesulfonamide (0.200 g, 0.719 mmol) in 1 mL DMF, and the mixture was stirred for 30 min. 4-Bromo-1-butene (0.2426 g, 1.80 mmol) in 2 mL DMF solution was added dropwise into the mixture and it was stirred at room temperature overnight. The reaction mixture was diluted with 30 mL EtOAc and washed with 1M HCl 2×10 mL and water 3×10 mL. The organic layer was dried over anhydrous Na2SO4 and evaporated to afford the crude product, which was subjected to silica gel chromatography using Hexanes/EtOAc to afford 0.1546 g white solid, yield 63.5%. was stirred at room temperature overnight washed with 1M HCl 2×10 mL and water 3×10 mL The organic layer was dried over anhydrous Na2SO4 evaporated to afford the crude product, which

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

Procedure: The title compound (8.0 g, 46%) was prepared from ethyl 2-(methylsulfonyl)propanoate (13.3 g, 74.1 mmol) and 4-bromobut-1-ene (10.0 g, 74.1 mmol) by following the procedure described for the synthesis of ethyl 2-methyl-2-(methylsulfonyl)hex-5-ynoate (Preparation 1, Step B). MS (GCMS) m/z 235 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ1.33 (t, J=7.17 Hz, 3H) 1.63 (s, 3H) 1.91-2.08 (m, 2H) 2.13-2.29 (m, 1H) 2.32 (d, J=7.51 Hz, 1H) 3.05 (s, 3H) 4.29 (q, J=7.06 Hz, 2H) 4.95-5.16 (m, 2H) 5.67-5.93 (m, 1H)

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

Procedure: 12 g Benzylamine and 25 g 4-bromo-1-buten were added to a suspension of 46 g potassium carbonate in 150 mL DMF and the mixture was heated at 50° C. for 16 h. The reaction mixture was cooled to RT, diluted with ethyl acetate, washed with water and brine, dried, concentrated, and purified by chromatographie on silica gel (hexane/ethyl acetate 50:1) to yield 18.3 g of the desired product. (M+H)+: 230 The reaction mixture was cooled to RT washed with water and brine dried concentrated purified by chromatographie on silica gel (hexane/ethyl acetate 50:1)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 7-hydroxycoumarin (3 g, 19.6 mmol) in DMF (20 ml) is treated with NaH (60% suspension in oil, 1.03 g, 25.9 mmol), then with 4-bromo-1-butene (2.65 g, 19.6 mmol). It is heated to 60° C. for 24 hours, then it is diluted with ethyl acetate (400 ml), and it is washed with water (3×300 mL) then with 1 M NaOH (3×200 ml). The residue is chromatographed with the mixture (ethyl acetate-hexane) to obtain 4-(7-coumarinyloxy)-1-butene (2.7 g, 67%). is washed with water (3×300 mL) The residue is chromatographed with the mixture (ethyl acetate-hexane)