Benzyl Bromide → 2-Amino-4-(benzyloxy)benzamide

HRID 625773Notes

Reaction equation

HRID 625773 reaction equation
[H-].[Na+].[NH2:3][C:4]1[CH:12]=[C:11]([OH:13])[CH:10]=[CH:9][C:5]=1[C:6]([NH2:8])=[O:7].[CH2:14](Br)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CN(C=O)C>[NH2:3][C:4]1[CH:12]=[C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:10]=[CH:9][C:5]=1[C:6]([NH2:8])=[O:7]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 205014282-Amino-4-hydroxybenzamide

Product 1

HCID 231302772-Amino-4-(benzyloxy)benzamideYield 43%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
15 °C

Procedure

To a solution of 95% NaH (1.82 g, 72.30 mmol) in DMF (100 mL) at 10° C. was added 2-amino-4-hydroxybenzamide (10.0 g, 66.72 mmol) in portions, maintaining the internal temperature at ca. 15° C. The cooling bath was removed, and the solution was allowed to warm to 40° C. over 25 min. The mixture was cooled to 10° C. and a solution of benzyl bromide (7.8 mL, 66.72 mmol) in DMF (20 mL) was added dropwise, and the mixture was allowed to warm to rt. After stirring for 20 h at rt, the mixture was cooled in an ice bath and quenched by addition of aq ammonium chloride. The solution was concentrated and diluted with water. The precipitate was collected by filtration, and the filtrate was extracted with EtOAc. The precipitate from above and the ethyl acetate extracts were combined and chromatographed on silica gel eluting with 20-80% EtOAc/DCM to afford 2-amino-4-(benzyloxy)benzamide as a solid (6.8 g, 43%). 1H NMR (300 MHz, DMSO-d6) δ ppm 5.04 (s, 2H) 6.14 (dd, J=8.76, 2.54 Hz, 1H) 6.27 (d, J=2.64 Hz, 1H) 6.71 (bs, 2H) 7.26-7.58 (m, 6H). LC-MS (ESI) m/z 243 (M+H)+.

Workup

  1. customThe cooling bath was removed
  2. temperatureto warm to 40° C. over 25 min
  3. temperatureThe mixture was cooled to 10° C.
  4. temperatureto warm to rt
  5. temperaturethe mixture was cooled in an ice bath
  6. customquenched by addition of aq ammonium chloride
  7. concentrationThe solution was concentrated
  8. additiondiluted with water
  9. filtrationThe precipitate was collected by filtration
  10. extractionthe filtrate was extracted with EtOAc
  11. customchromatographed on silica gel eluting with 20-80% EtOAc/DCM

Sources & evidence

ORD record
ord-277b9dcd01004cfab9bd3e7c31b57f70
Source dataset
uspto-grants-2016_04
Patent number
US09308207B2

Reaction notes

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