Methanol → HCID 83675281, compound

HRID 2174525Notes

Reaction equation

HRID 2174525 reaction equation
C([CH:3]([O-])[CH:4]=[CH:5][C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH3:16])=[CH:10][CH:9]=2)C.[H-].[H-].[H-].[H-].[Li+].[Al+3].C[OH:25]>C1COCC1.CCOC(C)=O.[Pd]>[OH:25][CH:4]([CH3:3])[CH2:5][C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH3:16])=[CH:10][CH:9]=2

Participants

7

Reactant 3

HCID 887MethanolHCID 21226445Aluminium lithium hydrideHCID 131732980HCID 131732980, compound

Product 1

HCID 83675281HCID 83675281, compoundYield 41%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Compound 429 (631 mg, 2.57 mmol) was dissolved in THF (20 mL) and stirred at 0° C. under Argon. 2 M LAH in THF (3 eq, 15 mL) was added dropwise. The resulting mixture was warmed to rt for 1 h and volatiles were evaporated in vacuo. The residue was carefully quenched with ice-cold 0.5 N HCl (200 mL) and then extracted with EtOAc (200 mL). The organic layer was separated and dried over Na2SO4. The resulting crude oil was purified by chromatography (30% to 70% EtOAc/hexanes) to provide a crude yellow solid, which demonstrated ˜85% purity based on 1H NMR. The impurity was determined to be a partially reduced alkene intermediate. The yellow solid was further reacted by dissolving in EtOAc (10 mL) and MeOH (10 mL) in a glass hydrogenation flask. 10% Pd/C (58 mg, 10% w/w) was added and the sample was hydrogenated for 4 h at 35 psi of H2 to ensure complete reduction. The mixture was filtered over Celite and purified by chromatography (20% to 70% EtOAc/hexanes) to yield a light-yellow solid (216 mg, 41%): mp 85-88° C. (lit.19 62-65° C.). TLC Rf 0.22 (50% EtOAc/hexanes). 1H NMR (600 MHz, CDCl3) δ 8.07 (s, 1H), 7.18-7.17 (d, 1H, J=8.7 Hz), 7.01 (d, 1H, J=2.4 Hz), 6.78-6.77 (dd, 1H, J1=8.7 Hz, J2=2.46 Hz), 6.19-6.18 (d, 1H, J=1.98 Hz), 3.84 (s, 3H), 3.75-3.73 (t, 2H, J=6.06 Hz), 2.87-2.85 (t, 2H, J=7.2 Hz), 1.97-1.94 (quin, 2H, J=6.12 Hz). 13C NMR (150 MHz, CDCl3) δ 154.2, 140.0, 131.2, 129.3, 111.16, 111.04, 102.1, 99.7, 62.3, 56.0, 31.9, 24.9. Elemental analysis for C12H15NO2: C, 70.22; H, 7.37; N, 6.82. Found: C, 70.10; H, 7.23; N, 6.74.

Workup

  1. temperatureThe resulting mixture was warmed to rt for 1 h
  2. customvolatiles were evaporated in vacuo
  3. customThe residue was carefully quenched with ice-cold 0.5 N HCl (200 mL)
  4. extractionextracted with EtOAc (200 mL)
  5. customThe organic layer was separated
  6. dry with materialdried over Na2SO4
  7. customThe resulting crude oil was purified by chromatography (30% to 70% EtOAc/hexanes)
  8. customto provide a crude yellow solid, which
  9. customThe yellow solid was further reacted
  10. filtrationThe mixture was filtered over Celite
  11. custompurified by chromatography (20% to 70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-a7e1e69f9cc54ce094611914d51fae06
Source dataset
uspto-grants-2015_06
Patent number
US09061994B1

Reaction notes

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