Nicotinate → 6-{[(1,1,1-Trifluoropropan-2-yl)oxy]methyl}pyridine-3-carboxylic acid

HRID 341516

反応式

HRID 341516 の反応式
[F:1][C:2]([F:7])([F:6])[CH:3]([OH:5])[CH3:4].[H-].[Na+].[N:10]1[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([O-:18])=[O:17])[CH:11]=1.[CH2:19]1COCC1>>[F:1][C:2]([F:7])([F:6])[CH:3]([O:5][CH2:19][C:15]1[N:10]=[CH:11][C:12]([C:16]([OH:18])=[O:17])=[CH:13][CH:14]=1)[CH3:4]

参加物

5

反応物 4

HCID 937Nicotinate2 回HCID 8028Tetrahydrofuran2 回HCID 97741,1,1-Trifluoro-2-propanolHCID 24758Sodium hydride

生成物 1

HCID 801526766-{[(1,1,1-Trifluoropropan-2-yl)oxy]methyl}pyridine-3-carboxylic acid収率 46%

実験手順

1,1,1-Trifluoropropan-2-ol (0.406 mL, 4.483 mmol) was added drop wise to a suspension of sodium hydride (60% in mineral oil) (0.239 g, 5.977 mmol) in dry THF (20 mL) at 0 C. The mixture was stirred at 0 C for 15 minutes. A solution of methyl 6-(methanesulfonyloxy)methyl]pyridine-3-carboxylate (Intermediate 189, 0.733 g, 2.989 mmol) in THF (10 mL) was added drop wise. The reaction mixture was stirred at 0 C for 30 minutes and room temperature for 3 days. The reaction mixture was quenched with water (10 mL) and diluted with EtOAc (30 mL). The phases were separated, and the organic phase was extracted with a saturated aqueous solution of sodium bicarbonate (3×15 mL). The aqueous extracts were combined, washed with EtOAc (1×10 mL). The organic phase was discarded and the aqueous phase was acidified to pH 4 using 2N HCl and extracted with EtOAc (3×30 mL). The organic extracts were combined, dried over sodium sulfate, filtered and evaporated to provide a brown crude residue. The crude material was purified by flash chromatography (DCM:MeOH 98:2) to afford the title compound as a beige solid (0.345 g, 46%). Method B HPLC-MS: MH+ requires m/z=250 Found: m/z=250, Rt=1.61 min (89%).

後処理

  1. stirringThe reaction mixture was stirred at 0 C for 30 minutes and room temperature for 3 days
  2. customThe reaction mixture was quenched with water (10 mL)
  3. additiondiluted with EtOAc (30 mL)
  4. customThe phases were separated
  5. extractionthe organic phase was extracted with a saturated aqueous solution of sodium bicarbonate (3×15 mL)
  6. washwashed with EtOAc (1×10 mL)
  7. extractionextracted with EtOAc (3×30 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customto provide a brown crude residue
  12. customThe crude material was purified by flash chromatography (DCM:MeOH 98:2)

出典と根拠

ORDレコード
ord-439caa1576984a4a87fdcc43cff79e51
出典データセット
uspto-grants-2014_11
特許番号
US08895733B2

関連ノート

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