Potassium tert-butoxide → HCID 58748233, compound

HRID 1162647Notes

Reaction equation

HRID 1162647 reaction equation
[CH3:1]C([O-])(C)C.[K+].[CH2:7]([O:9][C:10](=[O:27])[CH2:11][N:12]1[CH2:16][C:15](=O)[C@@H:14]([NH:18][C:19]([C:21]2[S:22][C:23]([Cl:26])=[CH:24][CH:25]=2)=[O:20])[CH2:13]1)[CH3:8]>C1COCC1.[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CCOC(C)=O>[CH2:7]([O:9][C:10](=[O:27])[CH2:11][N:12]1[CH2:16][C:15](=[CH2:1])[C@@H:14]([NH:18][C:19]([C:21]2[S:22][C:23]([Cl:26])=[CH:24][CH:25]=2)=[O:20])[CH2:13]1)[CH3:8]

Participants

6

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 58748248HCID 58748248, compound

Product 1

HCID 58748233HCID 58748233, compoundYield 76.5%

Reagents, catalysts & solvents 3

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

39.3 To a cooled (0° C.), stirred suspension of 44 mg potassium tert-butylate in 3 ml THF under an argon atmosphere were added 149 mg methyltriphenylphosphonium bromide. The yellow slurry was then stirred for 1 h 30, slowly warming up to room temperature. A solution of 100 mg {(S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-oxo-pyrrolidin-1-yl}-acetic acid ethyl ester in 2 ml THF was then added. The mixture was heated to reflux and stirred for 2 hrs. The mixture (dark brown slurry) was cooled to r.t., diluted with EtOAc, washed with sat. aq. NH4C1, H2O and brine, dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography (silica gel, gradient: CH2Cl2->CH2Cl2/MeOH 95:5) to give 76 mg {(R)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-methylene-pyrrolidin-1-yl}-acetic acid ethyl ester (contaminated with 43 w % triphenylphosphin oxide). Amorphous gum. MS 329.0 ([M+H]+)

Workup

  1. stirringThe yellow slurry was then stirred for 1 h 30
  2. temperatureslowly warming up to room temperature
  3. temperatureThe mixture was heated
  4. temperatureto reflux
  5. stirringstirred for 2 hrs
  6. temperatureThe mixture (dark brown slurry) was cooled to r.t.
  7. washwashed with sat. aq. NH4C1, H2O and brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product was purified by column chromatography (silica gel, gradient: CH2Cl2->CH2Cl2/MeOH 95:5)

Sources & evidence

ORD record
ord-c86c83d7ae9149d28da737eda6bd08e2
Source dataset
uspto-grants-2010_10
Patent number
US07820699B2

Reaction notes

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