Ammonium Chloride → Methyl 2-[3-(4-methoxymethylbenzyl)phenyl acetamido]-4-chlorobenzoate

HRID 2226520Notes

Reaction equation

HRID 2226520 reaction equation
Br[CH:2]([O:10]C(CC1C=CC=CC=1)Br)CC1C=CC=CC=1.[C:20]([Li])([CH3:23])([CH3:22])[CH3:21].[C:25]([Cu])#[C:26][CH2:27]CC.[Al].Br[CH2:33][C:34]1[CH:35]=[C:36]([CH2:40][C:41]([NH:43][C:44]2[CH:53]=[C:52]([Cl:54])[CH:51]=[CH:50][C:45]=2[C:46]([O:48][CH3:49])=[O:47])=[O:42])[CH:37]=[CH:38][CH:39]=1.[Cl-].[NH4+]>CCOCC.CCCCC.C1COCC1>[CH3:2][O:10][CH2:21][C:20]1[CH:23]=[CH:27][C:26]([CH2:33][C:34]2[CH:35]=[C:36]([CH2:40][C:41]([NH:43][C:44]3[CH:53]=[C:52]([Cl:54])[CH:51]=[CH:50][C:45]=3[C:46]([O:48][CH3:49])=[O:47])=[O:42])[CH:37]=[CH:38][CH:39]=2)=[CH:25][CH:22]=1

Participants

10

Reactant 6

HCID 25517Ammonium ChlorideHCID 5359268AluminumHCID 10408469HCID 10408469, compoundHCID 57221788HCID 57221788, compoundHCID 178418306HCID 178418306, compoundHCID 178445581HCID 178445581, compound

Product 1

HCID 54251663Methyl 2-[3-(4-methoxymethylbenzyl)phenyl acetamido]-4-chlorobenzoate

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent2×HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

The bromobenzylmethyl ether (2.28 g, 11.35 mmol) was dissolved in anhydrous ether (40 ml) and cooled to -78° C. with stirring under nitrogen. tert-Butyllithium (13.4 ml of a 1.7M solution in pentane, 22.7 mmol) was added dropwise over 5 mins, and stirring continued for 45 mins. This mixture was then cannulated into a suspension of pentynyl copper (1.48 g, 11.35 mmol) in anhydrous ether (40 ml) at -78° C. and allowed to warm to -40° C., with stirring under nitrogen. Light was excluded with aluminium foil. After 15 mins methyl 2-(3-bromomethylphenylacetamido)-4-chlorobenzoate (1.5 g, 3.78 mmol) was added as a solution in anhydrous THF (10 ml). The mixture was swirled manually as necessary. After stirring at -40° C. for 1.5 hours, the reaction was allowed to warm to room temperature and stirred for a further 1 hour. Saturated ammonium chloride solution was added and the mixture filtered through celite to remove copper residues. The organic layer was separated and washed with water and brine before drying (Na2SO4) and evaporating in vacuo to give a yellow oil. This was purified by flash chromatography eluting with 15% ethyl acetate in hexane to give methyl 2-[3-(4methoxymethylbenzyl)phenyl acetamido]-4-chlorobenzoate as a clear colourless oil (0.81 g, 1.85 mmol); δH (360 MHz, CDCl3) 3.36 (3H, s, CH2OCH3), 3.71 (2H, s, NHCOCH2), 3.84 (3H, s, COOCH3), 3.99 (2H, s, ArCH2Ar), 4.41 (2H, s, ArCH2O), 7.03 (1H, dd, J 8.6 and 2.1 Hz, 5-H), 7.10 (1H, d, J 7.5 Hz, Ar-H), 7.16-7.30 (7H, m, Ar-H), 7.91 (1H, d, J 8.6 Hz, 6-H), 8.81 (1H, d, J 2.1 Hz, 3-H), 11.06 (1H, br s, NH); m/z (EI+) 437 (M+).

Workup

  1. stirringstirring
  2. temperatureto warm to -40° C.
  3. stirringwith stirring under nitrogen
  4. stirringAfter stirring at -40° C. for 1.5 hours
  5. temperatureto warm to room temperature
  6. stirringstirred for a further 1 hour
  7. filtrationthe mixture filtered through celite
  8. customto remove copper residues
  9. customThe organic layer was separated
  10. washwashed with water and brine
  11. dry with materialbefore drying (Na2SO4)
  12. customevaporating in vacuo
  13. customto give a yellow oil
  14. customThis was purified by flash chromatography
  15. washeluting with 15% ethyl acetate in hexane

Sources & evidence

ORD record
ord-4489fc75d91a45088873e7629c7f679f
Source dataset
uspto-grants-1994_09
Patent number
US05348962

Reaction notes

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