Sodium hydride → methyl 4-[(2-{(5R)-2-oxo-5-[(1E)-3-oxooct-1-enyl] pyrrolidin-1-yl}ethyl)thio]-butanoate

HRID 22968

Reaction equation

HRID 22968 reaction equation
[H-].[Na+].[O:3]=[C:4]([CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:5]P(=O)(OC)OC.[CH:17]([C@H:19]1[CH2:23][CH2:22][C:21](=[O:24])[N:20]1[CH2:25][CH2:26][S:27][CH2:28][CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])=O>COCCOC>[O:24]=[C:21]1[CH2:22][CH2:23][C@H:19](/[CH:17]=[CH:5]/[C:4](=[O:3])[CH2:12][CH2:13][CH2:14][CH2:15][CH3:16])[N:20]1[CH2:25][CH2:26][S:27][CH2:28][CH2:29][CH2:30][C:31]([O:33][CH3:34])=[O:32]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 580181Dimethyl (2-oxoheptyl)phosphonateHCID 12132850HCID 12132850, compound

Product 1

HCID 12132851methyl 4-[(2-{(5R)-2-oxo-5-[(1E)-3-oxooct-1-enyl] pyrrolidin-1-yl}ethyl)thio]-butanoate

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of sodium hydride (95%, 14 mg, 0.58 mmol) in 3 mL of anhydrous 1,2-dimethoxyethane at 0° C. under an argon atmosphere was added dimethyl 2-oxoheptylphosphonate (ACROS, 0.13 mL, 0.61 mmol). The cooling bath was removed and the reaction was stirred for 2 hours. After this time period, the mixture was cooled to 0° C. and a solution of methyl 4-({2-[(2R)-2-formyl-5-oxopyrrolidin-1-yl]ethyl}thio)butanoate (0.55 mmol) in anhydrous 1,2-dimethoxyethane was added. The reaction was allowed to come to room temperature, stirred for 2 hours and then quenched with an aqueous solution of saturated ammonium chloride. Ethyl acetate (50 mL) was then added and the mixture was partitioned between the two phases. The organic solution was dried (brine, Na2SO4), evaporated via reduced pressure and purified with column chromatography (SiO2, EtOAc/Hexane-1/1) to yield methyl 4-[(2-{(5R)-2-oxo-5-[(1E)-3-oxooct-1-enyl]pyrrolidin-1-yl}ethyl)thio]-butanoate as an oil. This material was taken directly on to the next step.

Workup

  1. customThe cooling bath was removed
  2. customto come to room temperature
  3. stirringstirred for 2 hours
  4. customquenched with an aqueous solution of saturated ammonium chloride
  5. additionEthyl acetate (50 mL) was then added
  6. customthe mixture was partitioned between the two phases
  7. dry with materialThe organic solution was dried (brine, Na2SO4)
  8. customevaporated via reduced pressure
  9. custompurified with column chromatography (SiO2, EtOAc/Hexane-1/1)

Sources & evidence

ORD record
ord-7e43c2d28ad343ca94099f5a921f4bc6
Source dataset
uspto-grants-2005_02
Patent number
US06849657B2

Linked notes

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