Water → Methyl 4-(2-(3-(4-ethoxypiperidine-1-carbonyl)-4-fluorophenyl)acetyl)-1,2,5-trimethyl-1H-pyrrole-3-carboxylate

HRID 1091739Notes

Reaction equation

HRID 1091739 reaction equation
IC.[CH2:3]([O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]([C:14]2[CH:15]=[C:16]([CH2:21][C:22]([C:24]3[C:25]([C:31]([O:33][CH3:34])=[O:32])=[C:26]([CH3:30])[NH:27][C:28]=3[CH3:29])=[O:23])[CH:17]=[CH:18][C:19]=2[F:20])=[O:13])[CH2:8][CH2:7]1)[CH3:4].[C:35](=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[CH2:3]([O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]([C:14]2[CH:15]=[C:16]([CH2:21][C:22]([C:24]3[C:25]([C:31]([O:33][CH3:34])=[O:32])=[C:26]([CH3:30])[N:27]([CH3:35])[C:28]=3[CH3:29])=[O:23])[CH:17]=[CH:18][C:19]=2[F:20])=[O:13])[CH2:8][CH2:7]1)[CH3:4]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 57791805methyl 4-(2-(3-(4-ethoxypiperidine-1-carbonyl)-4-fluorophenyl)acetyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate

Product 1

HCID 57791827Methyl 4-(2-(3-(4-ethoxypiperidine-1-carbonyl)-4-fluorophenyl)acetyl)-1,2,5-trimethyl-1H-pyrrole-3-carboxylateYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Iodomethane (0.056 mL, 0.90 mmol) was added to methyl 4-(2-(3-(4-ethoxypiperidine-1-carbonyl)-4-fluorophenyl)acetyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate (53) (0.200 g, 0.45 mmol) and potassium carbonate (0.249 g, 1.80 mmol) in DMF (10 mL). The resulting suspension was stirred at room temperature for 2 hours. The reaction mixture was poured into water (75 mL) and extracted with EtOAc (3×50 mL). The combined organic layers were washed with water (50 mL) and saturated brine (50 mL). The organic layer was dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% ethyl acetate in isohexane. Pure fractions were evaporated to dryness to afford the desired material as a yellow gum (0.158 g, 77% yield); 1H NMR (400.132 MHz, CDCl3) δ 1.14 (3H, t), 1.43-1.65 (2H, m), 1.72 (1H, m), 1.85 (1H, m), 2.05 (3H, s), 2.38 (3H, s), 3.06 (1H, m), 3.32 (3H, s), 3.45 (5H, m), 3.74 (3H, s), 3.91 (2H, s), 3.99 (1H, m), 6.93 (1H, t), 7.08 (1H, m), 7.17 (1H, m); m/z (LC-MS, ESI+), RT=2.15 min (M+H=459.36).

Workup

  1. extractionextracted with EtOAc (3×50 mL)
  2. washThe combined organic layers were washed with water (50 mL) and saturated brine (50 mL)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customto afford crude product
  7. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 100% ethyl acetate in isohexane
  8. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-b4b97d01956e4a99a97c49878b28c1f9
Source dataset
uspto-grants-2012_03
Patent number
US08129380B2

Reaction notes

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