* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
5 Second Crop Crystallization of Ibuprofen Lysinate
EXAMPLE 5 Second Crop Crystallization of Ibuprofen Lysinate A molten mixture [stream 13, FIG. 2] containing S(+)-ibuprofen (0.2145 moles, 44.25 g), R(-)-ibuprofen (0.5763 moles, 118.89 g), and L-lysinate (0.08603 moles, 12.577 g) is added to heptane [350 g. stream 14a] heated to 50° C. The resulting mixture is stirred for fifteen minutes and then filtered at 50° C to remove precipitated ibuprofen lysinate from the mother liquor. The filtered solid is washed with heptane [50 g, stream 14b]. The mother and wash liquors are combined to provide a mixture [stream 15] containing S(+)-ibuprofen (0.1912 moles, 39.43 g) and R(-)-ibuprofen (0.5136 moles, 105.95 g). The washed filtered solid is a second crop of ibuprofen lysinate and is dissolved in a mixture [stream 23a] containing water (15 g), ethanol (76 g), and heptane (9 g).
5 Second Crop Crystallization of Ibuprofen Lysinate
EXAMPLE 5 Second Crop Crystallization of Ibuprofen Lysinate A molten mixture [stream 13, FIG. 2] containing S(+)-ibuprofen (0.2145 moles, 44.25 g), R(-)-ibuprofen (0.5763 moles, 118.89 g), and L-lysine (0.08603 moles, 12.577 g) is added to heptane [350 g, stream 14a] heated to 50° C. The resulting mixture is stirred for 15 minutes and then filtered at 50° C. to remove precipitated ibuprofen lysinate from the mother liquor. The filtered solid is washed with heptane [50 g, stream 14b]. The mother and wash liquors axe combined to provide a mixture [stream 15] containing S(+)-ibuprofen (0.1912 moles, 39.43 g) and R(-)-ibuprofen (0.5136 moles, 105.95 g). The washed filtered solid is a second crop of ibuprofen lysinate and is dissolved in a mixture [stream 23a] containing water (15 g), ethanol (76 g), and heptane (9 g).
5 Preparation of a reference granulate containing Ibuprofen lysinate
EXAMPLE 5 Preparation of a reference granulate containing Ibuprofen lysinate By working as described in Example 2 but substituting Ibuprofen arginate with an equivalent amount of Ibuprofen lysinate, sachets containing an amount of Ibuprofen corresponding to 800 mg, 400 mg or 600 mg were prepared.
2
[ 56-87-1 ]
[ 15687-27-1 ]
[ 57469-77-9 ]
Yield
Reaction Conditions
Operation in experiment
96 %
With pyrographite In ethanol; water Reflux;
1-3 Example 2:
Put 41.3g (0.200mol) of ibuprofen, 29.8g (0.204mol) of L-lysine (dried product), and 2.0g of activated carbon into 150ml of ethanol containing 2% water, heat up to reflux, and filter while hot. Wash the process with a small amount of ethanol, concentrate the filtrate to dryness under reduced pressure, add 50.0g of water, heat to dissolve; then add 500ml of n-heptane, heat up, reflux and divide water until no water is separated, continue to reflux and divide water for 1h; then cool down to Filter at room temperature, and wash the filter cake with a small amount of n-heptane; finally, dry it under reduced pressure at 60-65°C for 3 hours to obtain 67.7 g (0.192 mol) of off-white solid.After testing, the yield of the product was 96.0%