Hydrogen Peroxide → (3S,5R)-1-[4-(4-chlorophenoxy)phenyl]-5-[3-(trifluoromethyl)phenyl]-3-(3-hydroxypropyl)pyrrolidin-2-one

Temperature

0 °C

To a solution of (3S,5R)-1-[4-(4-chlorophenoxy)phenyl]-3-allyl-5-[3-(trifluoromethyl)phenyl]pyrrolidin-2-one (61.5 mg, 0.13 mmol) in dry THF (1 mL) at 0° C. and argon is added dropwise a 9-BBN solution (0.57 mL, 0.5 M in hexane). After the addition is complete, the reaction mixture is stirred at 0° C. for 2 h and at room temperature for 3 h. The mixture is then cooled to 0° C. and treated with a 3M NaOH (0.3 mL). The oxidation is carried out by slow addition of 35% H2O2 (0.3 mL) at 0° C. The reaction mixture is stirred at 0° C. for 1 h and then at room temperature overnight. The resulting solution is poured into ethyl acetate (50 mL), washed with brine (10 mL), dried over Na2SO4, filtered and evaporated. The residue is purified on silica gel (0-50% ethyl acetate in hexane) to give (3S,5R)-1-[4-(4-chlorophenoxy)phenyl]-5-[3-(trifluoromethyl)phenyl]-3-(3-hydroxypropyl)pyrrolidin-2-one (64 mg, 100%) as a colorless oil. 1H NMR (CDCl3, 400 MHz) δ 7.60-7.51 (m, 1H), 7.50-7.43 (m, 2H), 7.43-7.35 (m, 3H), 7.28-7.22 (m, 2H), 6.93-6.83 (m, 4H), 5.24 (dd, J=10.5, 3.0 Hz, 1H), 3.70 (t, J=7.2 Hz, 2H), 2.87-2.75 (m, 1H), 2.45-2.33 (m, 1H), 2.26-2.16 (m, 1H), 2.11-1.98 (m, 1H), 1.87 (s, br, 1H), 1.75-1.58 (m, 3H). HPLC-MS calculated for C26H23ClF3NO3 (M+H+) 490.13, found 490.10.

1. additionAfter the addition
2. temperatureThe mixture is then cooled to 0° C.
3. stirringThe reaction mixture is stirred at 0° C. for 1 h
4. customat room temperature
5. customovernight
6. washwashed with brine (10 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. customevaporated
10. customThe residue is purified on silica gel (0-50% ethyl acetate in hexane)

ORD record

ord-c4af994896c847f695325c3bcaba3a45

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08431607B2