Trifluoroacetic acid → 4-Bromo-3-hydroxypyridine

HRID 617301Notes

Reaction equation

HRID 617301 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.[Br: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>>[Br:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][C:17]=1[OH:22].[Br: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

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 11776TriphenylphosphineHCID 643448(S)-(-)-N-Boc-prolinolHCID 27624294-Bromo-3-hydroxypyridineHCID 5462977Diethyl azodicarboxylate

Product 2

HCID 27624294-Bromo-3-hydroxypyridineHCID 54424320HCID 54424320, compound

Procedure

(S)-1-t-Butoxycarbonyl-2-pyrrolidinemethanol (792 mg, 3.94 mmol), 4-bromo-3-pyridinol (685 mg, 3.94 mmol), DEAD (485 uL, 4.33 mmol) and PPh3 (1.14 g, 4.33 mmol) were allowed to react as described in Example 2a. The crude product was directly treated with trifluoroacetic acid (5 mL) at room temperature for 3 hours. The trifluoroacetic acid was removed under reduced pressure, and water (8 mL) was added. The mixture was extracted with EtOAc (2×20 mL), and the resultant aqueous layer was basified with excess solid sodium bicarbonate. The resultant slurry was washed extensively with EtOAc (4×10 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 (10:1.5:0.02 and 10:1.5:0.1) to provide 371 mg (37% yield from 4-bromo-3-pyridinol) of the title compound. TLC Rf 0.16 (10:1:0.02 CHCl3 /MeOH/NH4OH). MS (DCI/NH3) m/e 257 with 79Br and 259 (M+H)+ with 81Br. 1H NMR (CDCl3, 300 MHz) δ: 8.25 (s, 1H, ArH), 8.08 (d, J=6.6 Hz, 1H, ArH), 7.48 (d, J=6.6 Hz, 1H, ArH), 4.28 (dd, J=4.8, 10.2 Hz, 1H, OCHH), 4.17 (dd, J=6.3, 10.2 Hz, 1H, OCHH), 3.90-3.80 (m, 1H, NCH), 3.30-3.14 (m, 2H, NCH2), 2.18-1.80 (m, 4H, 2CH2).

Workup

  1. customto react
  2. customThe trifluoroacetic acid was removed under reduced pressure, and water (8 mL)
  3. additionwas added
  4. extractionThe mixture was extracted with EtOAc (2×20 mL)
  5. washThe resultant slurry was washed extensively with EtOAc (4×10 mL)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. customevaporated
  8. customThe crude product was purified by flash chromatography on silica gel eluting with CHCl3 /MeOH/NH4OH (10:1.5:0.02 and 10:1.5:0.1)

Sources & evidence

ORD record
ord-328aae7f8d0d4751bf06f2d7ed2ee2a7
Source dataset
uspto-grants-1999_09
Patent number
US05948793

Reaction notes

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