Ammonium Chloride → Methyl (S)-2-benzyloxycarbonylamino-4-oxopentanoate

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Reaction Conditions

Reaction Steps

Copper(I) bromide (60.9 g, 425 mmol, 1.2 equivalents (eq.)) was introduced into a 3 liter 4-neck flask (with dropping funnel, internal thermometer, argon inlet, rubber septa, in a cooling bath) and admixed with 250 ml of THF. A separate flask was initially charged at 10° C. with lithium bromide (75 g, 864 mmol, 2.4 eq.) and admixed with 470 ml of THF under argon. On completion of dissolution and recooling to RT, this solution was transferred to the suspension of the copper bromide. The resulting colorless to slightly greenish solution was cooled to −60° C., and methylmagnesium chloride (141 ml of a 3.0 M solution in THF, 423 mmol) was added within 15 min. A thick yellowish precipitate formed and the temperature rose to RT. After cooling again to −60° C., the solution from example 1 (prepared from 106 g of methyl (S)-2-benzyloxycarbonylamino-3-chlorocarbonylpropionate, 353 mmol, and 360 ml of THF) was added over about 30 min and the temperature was kept below −25° C. After the addition had ended, the mixture was stirred for another 1 h, and solid ammonium chloride (30 g) was added at −15° C. After a further 2 h, the mixture was filtered, the filtrate was diluted with 400 ml of heptane and 200 ml of saturated ammonium chloride solution were added. Once the mixture had been stirred at RT for 1 h, the organic phase was removed and washed repeatedly, and the aqueous phases were reextracted with ethyl acetate. The combined organic phases were dried over sodium sulfate, concentrated on a rotary evaporator under reduced pressure and chromatographed on 1 kg of silica gel with 1:3 to 1:1 ethyl acetate/heptane. After the products had been combined and dried under reduced pressure, 83 g (84% yield) of a white solid were obtained. 1H NMR (300 MHz, CDCl3): 7.4 (m, 5H); 5.78 (m, 1H); 5.18 (s, 2H); 4.6 (s, 1H); 3.75 (“s”, 3H); 3.3-2.9 (2dd, 2H); 2.2 (s, 3H)

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