bromomethyl acetate

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:

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

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

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

Procedure: A solution of 5-(N-Boc-amino)-5,7-dihydro-6H-dibenz[b,d]azepin-6-one (1.03, 3.08 mmol) (Example 7-E) in DMF was treated with Cs2CO3 (1.10 g, 3.39 mmol) and warmed to 60° C. To the reaction mixture was added bromomethyl acetate (0.321 ml, 3.39 mmol) (Aldrich) and stirring continued for 17 h. After cooling to 23° C. the mixture was diluted with CH2Cl2, washed with several portions of brine and dried over Na2SO4. The title compound was purified by chromatography (SiO2, CHCl3). After cooling to 23° C. the mixture washed with several portions of brine dried over Na2SO4 The title compound was purified by chromatography (SiO2, CHCl3)

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

Procedure: To a solution of Example 40D (100 mg, 0.22 mmol) in CH3CN (1.0 mL) was added K2CO3 (150 mg, 1.1 mmol) and bromomethyl acetate (20 μL, 0.22 mmol). The reaction solution was heated to reflux with stirring for 2 hours, cooled, diluted with ethyl acetate and poured into water. The organics were separated, dried (Na2SO4), filtered and concentrated by rotary evaporation. The residue was purified by reverse phase HPLC (water:acetonitrile; gradient of 5% to 90% acetonitrile) to provide the title compound (23 mg, 0.054 mmol, 24%). MS (ESI APCI) m/z 419.19 (M+H+); 1H NMR (300 MHz, DMSO-d6) δ 8.01 (s, 1H) 7.37 (d, J=8.82 Hz, 2H) 7.04 (d, J=9.19 Hz, 2H) 4.57-4.72 (m, 2H) 3.83 (bs, 2H) 3.66 (s, 3H) 1.57 (d, J=6.99 Hz, 3H) 1.29 (d, J=6.25 Hz, 6H). The reaction solution was heated to reflux cooled The organics were separated dried (Na2SO4) filtered concentrated by rotary evaporation The residue was purified by reverse phase HPLC (water:acetonitrile; gradient of 5% to 90% acetonitrile)

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution-of 60.2 mg of sodium (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(imidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate in 1.4 ml of DMF was added 67.7 mg of acetoxymethyl bromide under the atmosphere of argon at a temperature of −30° C., and the mixture was stirred for 3 hours during which the temperature was raised up to −10° C. The reaction mixture was diluted twice with 20 ml of ethy acetate, and washed twice with 10 ml of semi-saturated aqueous saline. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure to a volume of 2 ml. The residue thus obtained was purified by column chromatography on silica gel (dichloromethane:methanol=15:1) and Sephadex LH-20 (dichloromethane:methanol=1:1) in this sequence to give 22.1 mg of the title compound. washed twice with 10 ml of semi-saturated aqueous saline The organic layer was dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure to a volume of 2 ml The residue thus obtained was purified by column chromatography on silica gel (dichloromethane:methanol=15:1) and Sephadex

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 49 mg of sodium (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate in 1 ml of DMF was added 32 mg of acetoxymethyl bromide under the atmosphere of argon at −20° C., and the mixture was stirred for 3 hours during which the temperature was raised up to −10° C. The reaction mixture was extracted twice with 20 ml of ethyl acetate, and the organic layer was washed twice with 10 ml of semi-saturated aqueous saline, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to a volume of 2 ml. The residue thus obtained was purified by column chromatography on silica gel (chloroform:methanol=9:1) and on Sephadex LH-20 (dichloromethane:methanol=1:1) in this sequence to give 11 mg of the title compound. The reaction mixture was extracted twice with 20 ml of ethyl acetate the organic layer was washed twice with 10 ml of semi-saturated aqueous saline dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure to a volume of 2 ml The residue thus obtained was purified by column chromatography on silica gel (chloroform:methanol=9:1) and on Sephadex