Ethyl Acetate → HCID 86701718, compound

HRID 2174083Notes

Reaction equation

HRID 2174083 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]([C:22]3[C:30]([O:31][CH3:32])=[CH:29][C:28]([CH3:33])=[C:27]4[C:23]=3[CH:24]=[CH:25][N:26]4C([O-])=O)([O:16][CH2:17][C:18]([O:20]C)=[O:19])[C:12]([F:15])([F:14])[F:13])=[N:8][C:7]=2[CH:37]=1)#[N:2].[OH-].[Na+].OS([O-])(=O)=O.[K+].CCOC(C)=O>C1COCC1.CO.[Cl-].[Na+].O>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]([C:22]3[C:30]([O:31][CH3:32])=[CH:29][C:28]([CH3:33])=[C:27]4[C:23]=3[CH:24]=[CH:25][NH:26]4)([O:16][CH2:17][C:18]([OH:20])=[O:19])[C:12]([F:13])([F:14])[F:15])=[N:8][C:7]=2[CH:37]=1)#[N:2]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 14798Sodium Hydroxide2×HCID 516920Potassium bisulfateHCID 86701719HCID 86701719, compound

Product 1

HCID 86701718HCID 86701718, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of (±)-4-(1-(5-cyanobenzo[d]oxazol-2-yl)-2,2,2-trifluoro-1-(2-methoxy-2-oxoethoxy)ethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (90 mg, 0.157 mmol) in THF (1.5 mL) and MeOH (0.15 mL) was added 1 M aq. NaOH (0.47 mL, 0.47 mmol) and the reaction left to stir at rt for 1 h and then warmed up to 60° C. At this point, 2 M aq. NaOH (0.47 mL, 0.94 mmol) was added and the reaction mixture was stirred for 2 h. The reaction mixture was cooled to rt and diluted with 1M aq.KHSO4, brine and EtOAc. The organic layer was separated, dried over Na2SO4, filtered, and concentrated. The resulting residue was purified by RP-HPLC (HC-A) to give the title compound. 1H NMR (TFA salt, 400 MHz, CD3OD) δ ppm 8.21 (br. t, J=1.07 Hz, 1H), 7.80-7.81 (m, 2H), 7.35 (br. t, 1H), 6.82 (br. d, J=2.65 Hz, 1H), 6.72 (s, 1H), 4.32-4.46 (m, 2H) 3.20 (s, 3H), 2.54 (s, 3H). HRMS calcd. for C22H16F3N3O5 (M+H)+ 460.1120. found 460.1114.

Workup

  1. waitthe reaction left
  2. temperaturewarmed up to 60° C
  3. stirringthe reaction mixture was stirred for 2 h
  4. temperatureThe reaction mixture was cooled to rt
  5. additiondiluted with 1M aq
  6. customThe organic layer was separated
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified by RP-HPLC (HC-A)

Sources & evidence

ORD record
ord-371c5606e8954216ab5b19f9621310a5
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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