Sodium Hydroxide → HCID 86653767, compound

HRID 1528117Notes

Reaction equation

HRID 1528117 reaction equation
[CH2:1]([O:8][C:9]1[C:14]([CH3:15])=[C:13]([CH3:16])[C:12]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:11]([CH3:25])[C:10]=1[CH2:26][CH2:27][NH2:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:29](OC(OC(OC(C)(C)C)=O)=O)(C)(C)C.[OH-].[Na+]>O1CCOCC1.C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[C:14]([CH3:15])=[C:13]([CH3:16])[C:12]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:11]([CH3:25])[C:10]=1[CH2:26][CH2:27][NH:28][CH3:29])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 90495Di-tert-butyl dicarbonateHCID 86653768HCID 86653768, compound

Product 1

HCID 86653767HCID 86653767, compoundYield 87.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-(2,5-bis(benzyloxy)-3,4,6-trimethylphenyl)ethanamine (1.0 g, 2.65 mmol) in dioxane (6.6 mL) was added di-tert-butyldicarbonate (730 μL, 3.19 mmol), followed by aqueous sodium hydroxide (2.5 M solution, 1.28 mL, 3.19 mmol). The reaction mixture was stirred for 100 min, At this time, HPLC analysis indicated complete conversion to product. The mixture was then diluted in ethyl acetate (25 mL), transferred to a separatory funnel, and washed with 1 M aqueous sodium bicarbonate (2×10 mL), saturated ammonium chloride (10 mL), and brine (10 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The carbamate product was then dissolved in THF (13 mL), and the solution was treated with lithium aluminum hydride (800 mg). The resulting slurry was warmed to reflux and stirred for 90 min, after which HPLC analysis indicated consumption of starting material. The mixture was subsequently added slowly to 75 mL 2.5 M aqueous sodium hydroxide stirred over ice. The resulting grey suspension was stirred for 10 min, during which time the solids became white. To the suspension was added 100 mL isopropyl acetate, and the resulting mixture was filtered, and transferred to a separatory funnel. The organics were removed and the aqueous layer washed with 50 mL isopropyl acetate. The combined organics were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give 900 mg of 2-(2,5-bis(benzyloxy)-3,4,6-trimethylphenyl)-N-methylethanamine. 1H-NMR (400 MHz, CD3OD) 7.51-7.30 (m, 10H), 4.72 (s, 3H), 2.84 (s, 2H), 2.42 (m, 2H), 2.28 (s, 3H), 2.25 (s, 3H), 2.21 (s, 3H) ppm.

Workup

  1. customtransferred to a separatory funnel
  2. washwashed with 1 M aqueous sodium bicarbonate (2×10 mL), saturated ammonium chloride (10 mL), and brine (10 mL)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe carbamate product was then dissolved in THF (13 mL)
  7. additionthe solution was treated with lithium aluminum hydride (800 mg)
  8. temperatureThe resulting slurry was warmed
  9. temperatureto reflux
  10. stirringstirred for 90 min
  11. customconsumption of starting material
  12. additionThe mixture was subsequently added slowly to 75 mL 2.5 M aqueous sodium hydroxide
  13. stirringstirred over ice
  14. stirringThe resulting grey suspension was stirred for 10 min, during which time the solids
  15. additionTo the suspension was added 100 mL isopropyl acetate
  16. filtrationthe resulting mixture was filtered
  17. customtransferred to a separatory funnel
  18. customThe organics were removed
  19. washthe aqueous layer washed with 50 mL isopropyl acetate
  20. dry with materialThe combined organics were dried over anhydrous sodium sulfate
  21. filtrationfiltered
  22. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dfffe715802f4d8faeba9e7ea563e35c
Source dataset
uspto-grants-2015_07
Patent number
US09090576B2

Reaction notes

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