Trifluoroacetic anhydride → Pitavastatin Impurity 75

The reaction was terminated by the removal of cells by centrifuging at 4000×g for 20 minutes. The pH of the recovered cell-free supernatant was adjusted to 7.5 using 2M NaOH. MgSO4.1.6H2O (15% w/v based on anhydrous) was dissolved in the cell-free supernatant and the resulting solution was extracted twice with an equal volume of 2-pentanone. The solvent phases were collected and the solvent removed under reduced pressure in a rotary evaporator at 45° C. yielding an orange viscous oil. This was re-dissolved in 50 ml dry, distilled 2-pentanone and again the solvent was removed by rotary evaporation to afford t-butyl 3,5,6-trihydroxyhexanoate (5.08 g, 80% isolated yield). Diastereomeric excess was determined as follows; a sample of t-butyl 3,5,6-trihydroxyhexanoate (30 mg) was derivatised by reaction for at least 10 minutes at room temperature in an excess of trifluoroacetic anhydride, excess anhydride was removed under a stream of dry nitrogen and the residual oil diluted with dichloromethane (1 ml). The sample was analysed using a Chiralcel Dex CB column (25 meter) at a temperature of 140° C. (isothermal). The diastereomers eluted at 14.4 minutes (3R,5S diastereomer) and 15.7 minutes (3S,5S diastereomer). The diastereomeric excess of the sample was found by this method to be 99.7%.

1. customwas removed under a stream of dry nitrogen
2. additionthe residual oil diluted with dichloromethane (1 ml)
3. customat a temperature of 140° C. (isothermal)
4. washThe diastereomers eluted at 14.4 minutes (3R,5S diastereomer) and 15.7 minutes (3S,5S diastereomer)

ORD record

ord-b11c9283db304aad8117f891c14eff4d

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07157255B2