Acetic Acid → 1-[4-benzylmethylamino-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]ethanone

HRID 381507Notes

Reaction equation

HRID 381507 reaction equation
[CH2:1]([NH:8][C:9]1[CH:10]=[C:11](C(=O)C)[N:12]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C=O.[C:27]([BH3-])#N.[Na+].[C:31]([OH:34])(=O)[CH3:32]>CO>[CH2:2]([CH2:1][NH:8][C:9]1[CH:10]=[C:11]([C:31](=[O:34])[CH3:32])[N:12]([CH2:14][C:15]2[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=2)[CH:13]=1)[C:7]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:27]=1

Participants

6

Reactant 4

HCID 176Acetic Acid2×HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 183634051-[4-Benzylamino-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]ethanone

Product 1

HCID 183634121-[4-benzylmethylamino-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]ethanone

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a 100 mL round bottomed flask with a stirring bar and an addition funnel topped by an argon inlet was added 1-[4-benzylamino-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]ethanone AVIII-1-1 (0.472 g, 1.46 mmol), MeOH (20 mL), formalin (1.19 mL of 37% aqueous solution, 14.64 mmol) and sodium cyanoborohydride (0.628 g, 10.00 mmol). The addition funnel was charged with a solution of glacial acetic acid (0.57 mL, 10.0 mmol) in MeOH (20 mL). The acetic acid solution was added dropwise to the reaction mixture over 1.5 h. When the addition was complete, the resulting mixture was stirred at ambient temperature 18 h. The solvents were removed in vacuo and the residue was partitioned between EtOAc (100 mL) and water. The layers were separated and the organic phase was washed with saturated aqueous NaHCO3, aqueous sodium potassium tartrate and brine. Drying (MgSO4), filtration and removal of the solvent in vacuo gave an oil. This material was chromatographed on silica gel using 30% EtOAc in hexanes as eluant to give 1-[4-benzylmethylamino-1-(4-fluorobenzyl)-1H-pyrrol-2-yl]ethanone AVIII-2-1 as a crystalline solid. 1H NMR (CDCl3) δ 2.25 (3H, s), 2.36 (3H, s), 4.16 (2H, s), 5.43 (2H, s), 6.33 (1H, d, j=2.2 Hz), 6.53 (1H, d, j=2.2 Hz), 6.93 (2H, m), 7.06 (2H, m), 7.27 to 7.32 (5H, complex multiplet).

Workup

  1. customTo a 100 mL round bottomed flask with a stirring bar and an addition funnel topped by an argon inlet
  2. additionWhen the addition
  3. customThe solvents were removed in vacuo
  4. customthe residue was partitioned between EtOAc (100 mL) and water
  5. customThe layers were separated
  6. washthe organic phase was washed with saturated aqueous NaHCO3, aqueous sodium potassium tartrate and brine
  7. customDrying
  8. filtration(MgSO4), filtration and removal of the solvent in vacuo
  9. customgave an oil
  10. customThis material was chromatographed on silica gel using 30% EtOAc in hexanes as eluant

Sources & evidence

ORD record
ord-849f2dc87b3f43cfbb551d464b020b3b
Source dataset
uspto-grants-2001_10
Patent number
US06306891B1

Reaction notes

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