Trifluoroacetic acid → 4-Methylpyridin-3-ol

HRID 617306ノート

反応式

HRID 617306 の反応式
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][OH:14])=O)(C)(C)C.[CH3:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][C:17]=1[OH:22].CCOC(/N=N/C(OCC)=O)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.FC(F)(F)C(O)=O>C1COCC1>[CH3:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][C:17]=1[OH:22].[CH3:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][C:17]=1[O:14][CH2:13][C@@H:9]1[CH2:10][CH2:11][CH2:12][NH:8]1

参加物

8

反応物 5

HCID 6422Trifluoroacetic acidHCID 11776TriphenylphosphineHCID 643448(S)-(-)-N-Boc-prolinolHCID 27629084-Methylpyridin-3-olHCID 5462977Diethyl azodicarboxylate

生成物 2

HCID 27629084-Methylpyridin-3-olHCID 213097034-methyl-3-(2-(S)-pyrrolidinylmethoxy)pyridine

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

(S)-1-t-Butoxycarbonyl-2-pyrrolidinemethanol (590 mg, 2.94 mmol), 4-methyl-3-pyridinol (320 mg, 2.94 mmol), DEAD (509 uL, 3.23 mmol) and PPh3 (848 mg, 3.23 mmol) in THF (100 mL) were allowed to react as described in Example 2a. Solvent was removed, and the residue was chromatographed with CHCl3 /MeOH (10:1) to provide 1.8 g of the crude mixture. This material was immediately treated with trifluoroacetic acid (2.0 mL) at room temperature for 3 hours, and excess trifluoroacetic acid was removed under reduced pressure. Water (3 mL) and EtOAc (20 mL) were added, and the mixture was stirred for 5 minutes. The organic layer was decanted, and the residue washed with EtOAc (3×10 mL). The combined organic layers were dried (Na2SO4) and evaporated. The crude product was purified by flash chromatography on silica gel eluting with CHCl3 /MeOH/NH4OH (10:1:0.02 and 10:1.5:0.1) to provide 52 mg (14% yield from 4-methyl-3-pyridinol) of the title compound. TLC Rf 0.18 (10:1:0.02 CHCl3 /MeOH/NH40H). MS (DCI/NH3) m/e 193 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ: 8.16 (s, 1H, ArH), 8.12 (d, J=6.9 Hz, 1H, ArH), 7.07 (d, J=6.9 Hz, 1H, ArH), 4.12-4.00 (m, 2H, OCH2), 3.75-3.63 (m, 1H, NCH), 3.18-3.02 (m, 2H, NCH2), 2.24 (s, 3H, NCH3), 2.08-1.64 (m, 4H, 2CH2).

後処理

  1. customto react
  2. customSolvent was removed
  3. customthe residue was chromatographed with CHCl3 /MeOH (10:1)
  4. customto provide 1.8 g of the crude mixture
  5. customexcess trifluoroacetic acid was removed under reduced pressure
  6. additionWater (3 mL) and EtOAc (20 mL) were added
  7. customThe organic layer was decanted
  8. washthe residue washed with EtOAc (3×10 mL)
  9. dry with materialThe combined organic layers were dried (Na2SO4)
  10. customevaporated
  11. customThe crude product was purified by flash chromatography on silica gel eluting with CHCl3 /MeOH/NH4OH (10:1:0.02 and 10:1.5:0.1)

出典と根拠

ORDレコード
ord-9cf8f30056ee45d581da750f2408552a
出典データセット
uspto-grants-1999_09
特許番号
US05948793

反応ノート

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