Water → 4-(2-Benzylamino-1-methyl-ethyl)-phenol

HRID 130704Notes

Reaction equation

HRID 130704 reaction equation
[CH2:1]([NH:8][C:9](=O)[CH:10]([C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1)[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B.O1CCCC1.O.[OH-].[Na+]>O1CCCC1>[CH2:1]([NH:8][CH2:9][CH:10]([C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1)[CH3:11])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 2723981Borane;tetrahydrofuranHCID 22295290N-benzyl-2-(4-hydroxy-phenyl)-propionamide

Product 1

HCID 597303654-(2-Benzylamino-1-methyl-ethyl)-phenolYield 52.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Dissolve N-benzyl-2-(4-hydroxy-phenyl)-propionamide (13.25 g, 51.9 mmol) in anhydrous tetrahydrofuran (100 mL) and add via a cannula to borane-tetrahydrofuran complex (1.0M in tetrahydrofuran, 300 mL, 300 mmol) under nitrogen. Heat the reaction to reflux for 18 h under nitrogen. Cool the reaction to 0° C. and quench with 6 M hydrochloric acid. Concentrate the tetrahydrofuran on a rotary evaporator to give the crude product. Add water (50 mL) and tetrahydrofuran (30 mL) to the crude product and heat the reaction to reflux for 1 h. Cool the reaction to room temperature and adjust the pH to pH=8 with 5 N sodium hydroxide. Add brine (200 mL) and extract with ethyl acetate (3×200 mL). Dry the ethyl acetate extracts over magnesium sulfate, filter, and concentrate on a rotary evaporator to give the crude product. Purify the crude product by flash chromatography on silica gel eluting with 0.7% concentrated ammonium hydroxide/7% ethanol/chloroform to yield 6.55 g (52%) of 4-(2-benzylamino-1-methyl-ethyl)-phenol: HPLC (30/70 to 90/10 ACN/(0.1% TFA in water) Zorbax SB-Phenyl Column 4.6 mm×15 cm×5 micron: Retention time: 3.08 minutes, Purity: 99.6%; mass spectrum (ion spray): m/z=242.1 (M+1).

Workup

  1. temperatureHeat
  2. customthe reaction
  3. temperatureto reflux for 18 h under nitrogen
  4. temperatureCool
  5. customthe reaction to 0° C.
  6. customquench with 6 M hydrochloric acid
  7. concentrationConcentrate the tetrahydrofuran
  8. customon a rotary evaporator
  9. customto give the crude product
  10. customthe reaction
  11. temperatureto reflux for 1 h
  12. temperatureCool
  13. customthe reaction to room temperature
  14. extractionAdd brine (200 mL) and extract with ethyl acetate (3×200 mL)
  15. dry with materialDry the ethyl acetate
  16. filtrationfilter
  17. concentrationconcentrate on a rotary evaporator
  18. customto give the crude product
  19. customPurify the crude product by flash chromatography on silica gel eluting with 0.7% concentrated ammonium hydroxide/7% ethanol/chloroform

Sources & evidence

ORD record
ord-7f6afd815bdf4eb7a3ae5d5b2a19170a
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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