Reaction #87986

Reaction equation

methyl 7-((5R)-3,3-difluoro-5-((E)-4-methyl-3-oxooct-1-en-6-yn-1-yl)-2-oxopyrrolidin-1-yl)heptanoate

cerium chloride heptahydrate

Sodium borohydride

→

title compound

Yield 87.6%

methyl 7-((5R)-3,3-difluoro-5-((E)-3-hydroxy-4-methyloct-1-en-6-yn-1-yl)-2-oxopyrrolidin-1-yl)heptanoate

Yield 87.6%

Solvents

methanol

Conditions

Workup

1. 1
   OtherTo a −40° C.
2. 2
   workup.STIRRINGthe reaction was stirred for 3 hours
3. 3
   Otherquenched with equal parts water and saturated ammonium chloride
4. 4
   Temperaturewarmed to room temperature
5. 5
   ExtractionThe reaction mixture was extracted with ethyl acetate
6. 6
   DryingThe combined organic phase was dried over sodium sulfate
7. 7
   Concentrationconcentrated to a cloudy white oil
8. 8
   OtherThe residue was purified by silica gel chromatography
9. 9
   WashElution with methanol-dichloromethane (1:200 v:v)

Procedure

To a −40° C. solution consisting of methyl 7-((5R)-3,3-difluoro-5-((E)-4-methyl-3-oxooct-1-en-6-yn-1-yl)-2-oxopyrrolidin-1-yl)heptanoate (76 mg, 0.20 mmol) in methanol (5 mL) was added cerium chloride heptahydrate (75 mg, 0.20 mmol) in one portion. The reaction mixture was stirred for 15 minutes, and cooled to −78° C. for 20 minutes. Sodium borohydride (15 mg, 0.40 mmol) was added and the reaction was stirred for 3 hours, quenched with equal parts water and saturated ammonium chloride and warmed to room temperature. The reaction mixture was extracted with ethyl acetate. The combined organic phase was dried over sodium sulfate and concentrated to a cloudy white oil. The residue was purified by silica gel chromatography. Elution with methanol-dichloromethane (1:200 v:v) to afford the title compound (70 mg) as a clear oil. Rf 0.50 (solvent system: 5:95 v/v methanol:dichloromethane).

Source