Hydrochloric Acid → 5-Hydroxy-5-pyridin-3-ylbicyclo[2.2.2]octan-2-one

HRID 1809954Notes

Reaction equation

HRID 1809954 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2([OH:19])[CH2:16][CH:15]3[CH2:17][CH2:18][CH:8]2[CH2:9][C:10]23OCC[O:11]2)[CH:2]=1.Cl>C1COCC1.C([O-])(O)=O.[Na+].O>[OH:19][C:7]1([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[CH2:16][CH:15]2[CH2:17][CH2:18][CH:8]1[CH2:9][C:10]2=[O:11]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 595561105-Pyridin-3-ylspiro[bicyclo[2.2.2]octane-2,2'-[1,3]dioxolan]-5-ol

Product 1

HCID 595560585-Hydroxy-5-pyridin-3-ylbicyclo[2.2.2]octan-2-one

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 86585896Sodium bicarbonate waterSolvent

Procedure

Alcohol of step A (higher Rf isomer, 0.290 g, 1.11 mmol) was dissolved in THF (10 mL) under nitrogen. Hydrochloric acid (2.0 mL, 4.0 M aqueous solution, 8.0 mmol) was added and the mixture stirred for 4 hours at room temperature. The mixture was then diluted with NaHCO3/H2O and extracted twice with ethyl acetate. The extracts were washed with brine, dried over MgSO4, filtered and concentrated to provide a light yellow solid, 0.204 g (85%). The crude product 2 was used directly for the next step without further purification. 1H NMR (CDCl3) □δ□□ 8.74 (s, 1H), 8.52 (d, 1H), 7.72 (dt, 1H), 7.30 (dd, 1H), 2.66 (dt, 1H), 2.53 (m, 2H), 2.41 (t, 1H), 2.18 (t, 1H), 2.13 (d, 1H), 2.09 (m, 1H), 1.99 (m, 1H), 1.89 (m, 1H), 1.62 (m, 2H). Step C

Workup

  1. extractionextracted twice with ethyl acetate
  2. washThe extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto provide a light yellow solid, 0.204 g (85%)
  7. customThe crude product 2 was used directly for the next step without further purification

Sources & evidence

ORD record
ord-fe4f73b35da94248a0b07fc8d2ea3ca2
Source dataset
uspto-grants-2013_01
Patent number
US08362003B2

Reaction notes

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