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

HRID 1091739노트

반응식

HRID 1091739 반응식
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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-b4b97d01956e4a99a97c49878b28c1f9
출처 데이터셋
uspto-grants-2012_03
특허 번호
US08129380B2

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