N-methyl-N-(trimethylsilyl)trifluoroacetamide → (S)-[1-[[[[[[3-[[(1,4-Dihydro-5-hydroxy-4-oxo-2-pyridinyl)-carbonyl]amino]tetrahydro-2-oxo-1(2H)-pyrimidinyl]carbonyl]amino]-sulfonyl]amino]carbonyl]-2-oxo-3-azetidinyl]carbamic acid, phenylmethyl ester

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Reaction Steps

To a suspension of (S)-(2-oxo-3-azetidinyl)carbamic acid, phenylmethyl ester (6.61 g, 30.0 mmol) in 300 ml ethyl acetate chlorosulfonyl isocyanate (4.25 g, 30.0 mmol) was added, and the mixture was stirred for 1 hour at room temperature (solution A). To a solution of 3-[[(1,4-dihydro-5-hydroxy-4-oxo-2-pyridinyl)-carbonyl]-amino]tetrahydro-2-oxo-1(2H)-pyrimidinecarboxamide (8.86 g, 30.0 mmol) in 300 ml ethyl acetate, N-methyl-N-trimethylsilyltrifluoroacetamide (23.91 g, 120 mmol) was added. After 30 minutes a clear solution was obtained; 300 ml dichloromethane was added, followed by the dropwise addition of solution A at 0° C. After stirring overnight at room temperature 300 ml water was added whereupon an oily residue separated. The solvents were decanted off and the residue triturated with ether to give 10.27 g of the desired product (crude). The product was suspended in water and the pH adjusted to 6 with 2N sodium hydroxide. After freeze drying of the resulting solution the product was chromatographed in four portions on XAD under mplc conditions with water and water:acetonitrile 9:1 as eluents. The product-containing fractions were freeze dried to give a total of 5.2 g of the desired product.

Provenance & Evidence