Sodium Hydroxide → HCID 11845473, compound

HRID 1366928Notes

Reaction equation

HRID 1366928 reaction equation
[OH-].[Na+].C([O:5][C:6]([C:8]1[NH:9][CH:10]=[C:11]([CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[CH:12]=1)=[O:7])C>CO>[F:21][C:18]1[CH:17]=[CH:16][C:15]([CH2:14][CH2:13][C:11]2[CH:12]=[C:8]([C:6]([OH:7])=[O:5])[NH:9][CH:10]=2)=[CH:20][CH:19]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 57435103HCID 57435103, compound

Product 1

HCID 11845473HCID 11845473, compoundYield 84.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Freshly prepared aq. NaOH (10 M in H2O, 22.14 mmol) was added to a stirring, room temperature solution of 72 (1.1571 g, 4.428 mmol) in MeOH (11.1 mL, 0.4 M) under N2. The reaction was heated to reflux until the reaction was judged complete by HPLC (10 min). Upon cooling, the reaction solidified. The product was concentrated and then dissolved in H2O. The product was extracted with EtOAc, then the aqueous layer was made acidic (pH=2) with the dropwise addition of 10% aq. HCl. The product oiled out of solution, so EtOAc was added, and the organic layer was removed, dried with Na2SO4, filter, concentrated to obtain 73 (0.8724 g, 84.4%) as an off-white solid. The product was further purified by repeating the above procedure. The product was dissolved in 10% NaOH, washed with EtOAc, and then acidified with 10% HCl. As before, the product oiled out and was therefore extracted into EtOAc, dried with Na2SO4, filtered, and concentrated. 1H (CD3OD, 400 MHz): δ 7.14 (2H, dd, J=8.8, 5.4 Hz), 6.94 (2H, t, J=8.8 Hz), 6.68 (1H, d, J=1.7 Hz), 6.66 (1H, d, J=7.1 Hz), 2.82 (2H, t, J=7.3 Hz), 2.72 (2H, t, J=7.3 Hz) ppm. 13C (CD3OD, 100 MHz): δ 164.48, 162.69 (d, J=241 Hz), 139.28 (d, J=3.2 Hz), 131.08 (d, J=8.2 Hz), 126.08, 123.47, 122.68, 116.41, 115.68 (d, J=21.0 Hz), 37.77, 29.94 ppm. DEPT (CDCl3, 100 MHz): CH2 carbons: 37.77, 29.94; CH carbons: 131.08 (d, J=8.2 Hz), 122.68, 116.41, 115.68 (d, J=21.0 Hz) ppm. HPLC: 9.575 min.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux until the reaction
  3. customwas judged complete by HPLC (10 min)
  4. temperatureUpon cooling
  5. concentrationThe product was concentrated
  6. dissolutiondissolved in H2O
  7. extractionThe product was extracted with EtOAc
  8. additionwith the dropwise addition of 10% aq. HCl
  9. additionwas added
  10. customthe organic layer was removed
  11. dry with materialdried with Na2SO4
  12. filtrationfilter
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-fc6a652ebc9245ebb0a3bcaf1a8816f5
Source dataset
uspto-grants-2011_02
Patent number
US07893098B2

Reaction notes

Loading…