Sodium borohydride → (3R,5R)-1-[4-(4-chlorophenoxy)phenyl]-5-[3-(trifluoromethyl)phenyl]-3-(2-hydroxyethyl)pyrrolidin-2-one

HRID 1972249Notes

Reaction equation

HRID 1972249 reaction equation
[Cl:1][C:2]1[CH:33]=[CH:32][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([N:13]3[C@@H:17]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=4)[CH2:16][C@H:15]([CH2:28][CH:29]=C)[C:14]3=[O:31])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[BH4-].[Na+].C(Cl)Cl.C[OH:40]>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]2[CH:8]=[CH:9][C:10]([N:13]3[C@@H:17]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:25])([F:27])[F:26])[CH:19]=4)[CH2:16][C@H:15]([CH2:28][CH2:29][OH:40])[C:14]3=[O:31])=[CH:11][CH:12]=2)=[CH:32][CH:33]=1

Participants

4

Reactant 3

HCID 4311764Sodium borohydrideHCID 21226129Dichloromethane methanolHCID 59485752(3S,5R)-1-[4-(4-chlorophenoxy)phenyl]-3-allyl-5-[3-(trifluoromethyl) phenyl]pyrrolidin-2-one

Product 1

HCID 59485589(3R,5R)-1-[4-(4-chlorophenoxy)phenyl]-5-[3-(trifluoromethyl)phenyl]-3-(2-hydroxyethyl)pyrrolidin-2-oneYield 89%

Conditions

Temperature
-78 °C

Procedure

(3S,5R)-1-[4-(4-chlorophenoxy)phenyl]-3-allyl-5-[3-(trifluoromethyl)phenyl]pyrrolidin-2-one (56 mg, 0.119 mmol) is dissolved in 3 mL of a 2:1 mixture of CH2Cl2-MeOH and is cooled to −78° C. Ozone is bubbled through the solution until a blue color persisted and then nitrogen is bubbled through until it is clear. NaBH4 (2.5 eq) is added and the reaction mixture is allowed to warm to room temperature. The mixture is stirred for 2 h, and then most of the solvent is removed by evaporation in vacuo. Water is added (10 mL) and the aqueous layer is extracted with ethyl acetate (5×10 mL). The combined extracts are washed with brine (10 mL), dried over Na2SO4, filtered and evaporated. The residue is purified on silica gel (0-55% ethyl acetate in hexane) to give (3R,5R)-1-[4-(4-chlorophenoxy)phenyl]-5-[3-(trifluoromethyl)phenyl]-3-(2-hydroxyethyl)pyrrolidin-2-one (51 mg, 89%) as a colorless oil. 1H NMR (CDCl3, 400 MHz) δ 7.51-7.46 (m, 1H), 7.44-7.37 (m, 2H), 7.36-7.30 (m, 3H), 7.21-7.16 (m, 2H), 6.87-6.78 (m, 4H), 5.21 (dd, J=10.5, 2.0 Hz, 1H), 3.85-3.68 (m, 2H), 2.97-2.85 (m, 1H), 2.45-2.32 (m, 1H), 2.26-2.15 (m, 2H), 2.10-1.98 (m, 1H), 1.80-1.69 (m, 1H). HPLC-MS calculated for C25H21ClF3NO3 (M+H+) 476.12, found 476.10.

Workup

  1. customOzone is bubbled through the solution until a blue color
  2. customnitrogen is bubbled through until it
  3. temperatureto warm to room temperature
  4. custommost of the solvent is removed by evaporation in vacuo
  5. additionWater is added (10 mL)
  6. extractionthe aqueous layer is extracted with ethyl acetate (5×10 mL)
  7. washThe combined extracts are washed with brine (10 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue is purified on silica gel (0-55% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-784f534b58ed42a088243b13ad302d97
Source dataset
uspto-grants-2013_04
Patent number
US08431607B2

Reaction notes

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