iodomethyl propan-2-yl carbonate

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: In the same manner as in Example 81, 203 mg of the title compound was prepared from 348 mg of sodium (1R,5S,6S)-6-((1R)-1-hydroxyethyl)-2-[[(Z)-2-(4-hydroxymethylthiazol-5-yl)ethen-1-yl]thio]-1-methyl-1-carbapen-2-em-3-carboxylate and 252 mg of isopropyloxycarbonyloxymethyl iodide.

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

Procedure: The title compound was prepared from iodomethyl 1-methylethyl carbonate (140 mg, 0.574 mmol), 1b (50 mg, 0.117 mmol), potassium carbonate (48 mg, 0.351 mmol), and tetrabutylammonium hydrogen sulfate (40 mg, 0.117 mmol), using a similar process to that described in example 1. 1H NMR (CDCl3) δ 10.29 (m, 1H), 8.44 (s, 1H), 7.29 (m, 1H), 6.77 (m, 2H), 5.84 (s, 2H), 5.27 (dd, J=9.6, 3.6 Hz, 1H), 4.88 (m, 1H), 4.56 (m, 2H), 4.40-4.29 (m, 3H), 3.89 (m, 1H), 3.65 (m, 1H), 1.37 (d, J=6.4 Hz, 3H) 1.26 (m, 6H). ES+ MS: 522 (M+1).

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

Procedure: To (+)-3-hydroxy-N-(benzyloxycarbonyl)morphinan (33.0 g, 87.4 mmol) and cesium carbonate (28.5 g, 87.4 mmol) in acetone (450 mL) was added iodomethyl isopropyl carbonate (21.3 g, 87.4 mmol) (see Rigel Pharmaceuticals, Inc. US2006/247287 A1, Appl.; US2006-381215 (2006 May 2)) at room temperature. The reaction mixture was stirred vigorously at room temperature overnight. The acetone was then removed by rotary evaporation under vacuum. To the residue was added saturated NaHCO3 solution. The mixture was extracted with EtOAc (300 mL×2). The combined organics were washed with 1N HCl solution (300 mL), dried over MgSO4, filtered, and evaporated under vacuum to provide the title compound (42.0 g, 97%) as a yellow gum. The acetone was then removed by rotary evaporation under vacuum To the residue was added saturated NaHCO3 solution The mixture was extracted with EtOAc (300 mL×2) The combined organics were washed with 1N HCl solution (300 mL) dried over MgSO4 filtered evaporated under vacuum

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

Procedure: Following the general procedure for the preparation of acyloxyalkyl/alkoxycarbonyloxyalkyl carboxylic esters from carboxylic acids of Description 22, (2R)-4-[(3-chloropropyl)sulfonyloxy]-3,3-dimethyl-2-(phenylmethoxy)butanoic acid (11) (0.3 g, 0.79 mmol) dissolved in 5 mL of anhydrous toluene was reacted with 0.58 g (2.4 mmol) of methylethyl (iodomethoxy)formate in the presence of 0.27 g (1.0 mmol) of silver carbonate (Ag2CO3). After work-up, the crude material was purified by silica gel column chromatography using a mixture of ethyl acetate (EtOAc) and hexane (Hxn) (EtOAc/Hxn=1:2) as eluent to provide 0.14 g (36% yield) of the title compound (27a) as a colorless oil. Rf=0.59 (EtOAc/Hxn=1:2). 1H NMR (400 MHz, CDCl3): δ=1.07 (s, 3H), 1.08 (s, 3H), 1.31-1.34 (m, 6H), 2.25-2.32 (m, 2H), 3.32-3.36 (m, 2H), 3.63-3.65 (m, 2H), 3.90 (s, 1H), 3.96 (d, J=9.2 Hz, 1H), 4.21 (d, J=9.6 Hz, 1H), 4.37 (d, J=11.2 Hz, 1H), 4.64 (d, J=11.2 Hz, 1H), 4.89-4.95 (m, 1H), 5.78 (d, J=5.6 Hz, 1H), 5.87 (d, J=5.6 Hz, 1H), 7.30-7.37 (m, 5H) ppm. MS (ESI) m/z 495.02 (M+H)+, 516.98 (M+Na)+. The analytical data was consistent with the proposed structure. After work-up, the crude material was purified by silica gel column chromatography a mixture of ethyl acetate (EtOAc) and hexane (Hxn) (EtOAc/Hxn=1:2) as eluent

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

Procedure: In the same manner as in Example 81, 203 mg of the title compound was prepared from 348 mg of sodium (1R,5S,6S)-6-((1R)-1-hydroxyethyl)-2-[[(Z)-2-(4-hydroxymethylthiazol-5-yl)ethen-1-yl]thio]-1-methyl-1-carbapen-2-em-3-carboxylate and 252 mg of isopropyloxycarbonyloxymethyl iodide.

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

Procedure: The title compound was prepared from iodomethyl 1-methylethyl carbonate (140 mg, 0.574 mmol), 1b (50 mg, 0.117 mmol), potassium carbonate (48 mg, 0.351 mmol), and tetrabutylammonium hydrogen sulfate (40 mg, 0.117 mmol), using a similar process to that described in example 1. 1H NMR (CDCl3) δ 10.29 (m, 1H), 8.44 (s, 1H), 7.29 (m, 1H), 6.77 (m, 2H), 5.84 (s, 2H), 5.27 (dd, J=9.6, 3.6 Hz, 1H), 4.88 (m, 1H), 4.56 (m, 2H), 4.40-4.29 (m, 3H), 3.89 (m, 1H), 3.65 (m, 1H), 1.37 (d, J=6.4 Hz, 3H) 1.26 (m, 6H). ES+ MS: 522 (M+1).