4-Bromobutyryl chloride → HCID 69543859, compound

Participants

Reaction Steps

(step 27) To 150 mg (0.25 mmol) (2S,4R)-1-(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acid hydrazide in 65 ml THF were added 52 μl (0.3 mmol, 1.2 eq) iPr2EtN and 29 μl (0.25 mmol) 4-bromobutyryl chloride at 0° C. The solution was stirred at RT for 2 h, the solution was concentrated and redissolved in ethyl acetate/H2O. The inorganic phase was extracted with ethyl acetate and, the organic phase was washed with brine and dried over Na2SO4. Column chromatography with ethyl acetate:hexane 1:1 yields 170 mg (92%) (2S,4R)-1(Naphthalene-2-sulfonyl)-4-tritylsulfanyl-pyrrolidine-2-carboxylic acid N′-(4-bromo-butyryl)-hydrazide which was dissolved in 120 ml DMF and treated with 17 mg (0.38 mmol, 55% in mineral oil). NaH and the solution stirred for 2 h, was concentrated and dissolved in ethyl acetate/H2O. The inorganic phase was extracted with ethyl acetate, the organic phase washed with brine and dried over Na2SO4. The crude product was purified by column chromatography yielding 75 mg (45%) (2S,4R)-4-tritylsulfanyl -1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid (2-oxo-pyrrolidin-1-yl)-amide as white foam and 40 mg (25%) (2S,4R)-1-[4-tritylsulfanyl-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carbonyl]-tetrahydro-pyridazin-3-one as white foam. The two compounds were treated separately in TFA (2 ml/mmol tritylsulfanyl) with 10 eq triethylsilane at 0° C. to RT, until no educt could be detected, to yield (2S,4R)-4-Mercapto-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid (2-oxo-pyrrolidin-1-yl)-amide as white foam, MS: 420 (MH+) and (2S,4R)-1-[4-Mercapto-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carbonyl]-tetrahydro-pyridazin-3-one as white foam, MS: 420 (MH+), respectively.

Provenance & Evidence