Trifluoroacetic acid → 4-Methylpyridin-3-ol

HRID 617306Notes

Reaction equation

HRID 617306 reaction equation
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

Participants

8

Reactant 5

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

Product 2

HCID 27629084-Methylpyridin-3-olHCID 21309703HCID 21309703, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(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).

Workup

  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)

Sources & evidence

ORD record
ord-9cf8f30056ee45d581da750f2408552a
Source dataset
uspto-grants-1999_09
Patent number
US05948793

Reaction notes

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