Triethylamine → HCID 11774823, compound

HRID 625892Notes

Reaction equation

HRID 625892 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10](/[CH:17]=[CH:18]/[C:19]([OH:21])=O)=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.C(Cl)(=O)C(C)(C)C.C([Li])CCC.[Li].[C:42]1([C@@H:48]2[CH2:52][O:51][C:50](=[O:53])[NH:49]2)[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>C1COCC1>[O:21]=[C:19]([N:49]1[C@H:48]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH2:52][O:51][C:50]1=[O:53])/[CH:18]=[CH:17]/[C:10]1[C:11]2[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH:9]=1

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 730425(4R)-4-phenyl-1,3-oxazolidin-2-one2×HCID 3028194LithiumHCID 11323657HCID 11323657, compoundHCID 178418339Butyllithium2×

Product 1

HCID 11774823HCID 11774823, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of (E)-3-(1-(tert-butoxycarbonyl)-1H-indol-3-yl)acrylic acid (7.14 g, 24.85 mmol) in THF (400 mL) at −78° C. were added Et3N (10.39 ml, 74.6 mmol) and pivaloyl chloride (6.12 ml, 49.7 mmol). The mixture was stirred for 15 min at −78° C. then warmed to 0° C. for 1.5 h. The mixture was cooled to −78° C., to which was added n-Butyllithium (1.6 M in Hexanes)(14 mL, 22.4 mmol), then added the lithium salt of (R)-4-phenyl-2-oxazolidinone [prepared by adding n-Butyllithium (1.6 M in Hexanes)(31 ml, 49.7 mmol), to a solution of (R)-4-phenyloxazolidin-2-one (8.11 g, 49.7 mmol)] in THF (200 mL) at −78° C.) via cannula. The reaction was stirred at −78° C. for 2 h then at rt for 16 h. The reaction was quenched with saturated NH4Cl aqueous solution. The organics were removed under vacuum and the aqueous was extracted with EtOAc. The organic layer was collected, washed with brine, dried over sodium sulfate, and concentrated under vacuum. The crude product was purified by silica gel chromatography using a gradient of 10-20% EtOAc/Hexanes. The product fractions were collected and the solvent removed under vacuum to give ((R,E)-tert-butyl 3-(3-oxo-3-(2-oxo-4-phenyloxazolidin-3-yl)prop-1-en-1-yl)-1H-indole-1-carboxylate, 7.12 g (66%). ESI-MS (+) m/z 433.4 (M+1).

Workup

  1. temperaturethen warmed to 0° C. for 1.5 h
  2. temperatureThe mixture was cooled to −78° C., to which
  3. customprepared
  4. customat −78° C.
  5. stirringThe reaction was stirred at −78° C. for 2 h
  6. waitat rt for 16 h
  7. customThe reaction was quenched with saturated NH4Cl aqueous solution
  8. customThe organics were removed under vacuum
  9. extractionthe aqueous was extracted with EtOAc
  10. customThe organic layer was collected
  11. washwashed with brine
  12. dry with materialdried over sodium sulfate
  13. concentrationconcentrated under vacuum
  14. customThe crude product was purified by silica gel chromatography
  15. customThe product fractions were collected
  16. customthe solvent removed under vacuum

Sources & evidence

ORD record
ord-0c8341bb7dc848498150d67cc2ec12db
Source dataset
uspto-grants-2016_04
Patent number
US09308236B2

Reaction notes

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