Acetic Acid → (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-3-(2-hydroxyethyl)-3-(2-morpholinoethyl)piperidin-2-one

A mixture of 94 mg (0.15 mmol) of crude 2-((5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-2-oxo-3-(2-(triisopropylsilyloxy)ethyl)piperidin-3-yl)acetaldehyde (Example 69, Step B, mixture of diastereomers), 66 μL (0.76 mmol) of morpholine, 97 mg (0.46 mmol) of sodium triacetoxyborohydride and 30 μL (0.53 mmol) of acetic acid was suspended in a mixture of 1,2-dichloroethane (6 mL) and DMF (2 mL). After being stirred at room temperature for 20 h, the reaction mixture was quenched with saturated aqueous sodium bicarbonate and extracted with DCM (3×). The combined organic layers were dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by reversed phase preparatory HPLC (SunFire™ Prep C18 OBD 10 μm column (Waters, Milford, Mass.), gradient elution of 50% MeCN in water to 90% MeCN in water over a 30 min period, where both solvents contain 0.1% TFA) provided the title compound (mixture of C-3 epimers) along with the corresponding TIPS ether (mixture of C-3 epimers) and the corresponding trifluoroacetate (mixture of C-3 epimers) as a colorless oil.

1. customthe reaction mixture was quenched with saturated aqueous sodium bicarbonate
2. extractionextracted with DCM (3×)
3. dry with materialThe combined organic layers were dried over Na2SO4
4. filtrationfiltered
5. concentrationthe filtrate was concentrated
6. customPurification of the residue by reversed phase preparatory HPLC (SunFire™ Prep
7. washC18 OBD 10 μm column (Waters, Milford, Mass.), gradient elution of 50% MeCN in water to 90% MeCN in water over a 30 min period, where both solvents

ORDレコード

ord-3557e0d16e544ba29127e13f7ea6fe6a

出典データセット

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09296736B2