Tetrahydrofuran → HCID 68069072, compound

HRID 1184440Notes

Reaction equation

HRID 1184440 reaction equation
CC([O-:5])(C)C.[K+].[CH3:7][CH:8]1[O:13][C:12]2[CH:14]=[CH:15][C:16]([CH:18]=O)=[CH:17][C:11]=2[NH:10][C:9]1=[O:20].[CH2:21]1[CH2:25][O:24][CH2:23][CH2:22]1>>[CH3:7][CH:8]1[O:13][C:12]2[CH:14]=[CH:15][C:16](/[CH:18]=[CH:22]/[C:23]([O:24][CH2:25][CH3:21])=[O:5])=[CH:17][C:11]=2[NH:10][C:9]1=[O:20]

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 218738872-methyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbaldehydeHCID 23665647Potassium tert-butoxide

Product 1

HCID 68069072HCID 68069072, compoundYield 92%

Conditions

Temperature
0 °C

Procedure

In a 100 mL round bottom flask equipped with a magnetic stir bar was added t-BuOK (352 mg, 3.14 mmol) and THF (5 mL). The solution was cooled to 0° C. Triethylphosphonoacetate (0.576 mL, 2.88 mmol) was added slowly by syringe pump over 30 min. Using 13 (500 mg, 2.62 mmol) in THF (5 mL), the aldehyde was added via syringe pump over 30 min at 0° C. When the addition was complete, the reaction was warmed to room temperature and stirred for 2 h. The reaction was quenched with sat aqueous NH4Cl (10 mL) and extracted with EtOAc. The organic layer was washed with brine, dried (MgSO4) and concentrated in vacuo. The residue was purified by flash column chromatography using a gradient of 25-50% EtOAc in hexanes. The appropriate fractions were combined and concentrated in vacuo to give the title compound as a white solid (631 mg, 92% yield): 1H NMR (400 MHz, DMSO-d6) δ ppm 1.25 (t, J=7.20 Hz, 3H) 1.43 (d, J=6.82 Hz, 3H) 4.18 (q, J=7.16 Hz, 2H) 4.70-4.77 (m, 1H) 6.38 (d, J=15.92 Hz, 1H) 7.13 (d, J=2.02 Hz, 1H) 7.33 (dd, J=8.72, 2.15 Hz, 1H) 7.56 (d, J=15.92 Hz, 1H) 10.78 (s, 1H). ESI-MS: m/z 262.2 (M+H)+.

Workup

  1. customIn a 100 mL round bottom flask equipped with a magnetic stir bar
  2. additionWhen the addition
  3. temperaturethe reaction was warmed to room temperature
  4. customThe reaction was quenched with sat aqueous NH4Cl (10 mL)
  5. extractionextracted with EtOAc
  6. washThe organic layer was washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash column chromatography
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-21b17d75868f4748bacc269d4a6cce07
Source dataset
uspto-grants-2014_03
Patent number
US08669249B2

Reaction notes

Loading…