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

HRID 709115Notes

Reaction equation

HRID 709115 reaction equation
[F:1][C:2]1([F:28])[CH2:6][C@H:5](/[CH:7]=[CH:8]/[C:9](=[O:16])[CH:10]([CH3:15])[CH2:11][C:12]#[C:13][CH3:14])[N:4]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([O:25][CH3:26])=[O:24])[C:3]1=[O:27].O.O.O.O.O.O.O.[Cl-].[Ce+3].[Cl-].[Cl-].[BH4-].[Na+]>CO>[F:28][C:2]1([F:1])[CH2:6][C@H:5](/[CH:7]=[CH:8]/[CH:9]([OH:16])[CH:10]([CH3:15])[CH2:11][C:12]#[C:13][CH3:14])[N:4]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([O:25][CH3:26])=[O:24])[C:3]1=[O:27]

Participants

5

Reactant 3

HCID 4311764Sodium borohydrideHCID 21585214Cerium trichloride heptahydrateHCID 90054438methyl 7-((5R)-3,3-difluoro-5-((E)-4-methyl-3-oxooct-1-en-6-yn-1-yl)-2-oxopyrrolidin-1-yl)heptanoate

Product 1

HCID 72949021methyl 7-((5R)-3,3-difluoro-5-((E)-3-hydroxy-4-methyloct-1-en-6-yn-1-yl)-2-oxopyrrolidin-1-yl)heptanoateYield 87.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-78 °C

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).

Workup

  1. customTo a −40° C.
  2. stirringthe reaction was stirred for 3 hours
  3. customquenched with equal parts water and saturated ammonium chloride
  4. temperaturewarmed to room temperature
  5. extractionThe reaction mixture was extracted with ethyl acetate
  6. dry with materialThe combined organic phase was dried over sodium sulfate
  7. concentrationconcentrated to a cloudy white oil
  8. customThe residue was purified by silica gel chromatography
  9. washElution with methanol-dichloromethane (1:200 v:v)

Sources & evidence

ORD record
ord-6283836f0cad424cb914f5b0921e7825
Source dataset
uspto-grants-2015_11
Patent number
US09180116B2

Reaction notes

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