Hydrochloric Acid → HCID 67281686, compound

HRID 913025Notes

Reaction equation

HRID 913025 reaction equation
C([O:8][C:9]1[C:14](=[O:15])[CH:13]=[C:12]([CH:16]([OH:21])[C:17]([F:20])([F:19])[F:18])[N:11]([CH3:22])[C:10]=1[CH3:23])C1C=CC=CC=1.Cl>[Pd].CO>[OH:8][C:9]1[C:14](=[O:15])[CH:13]=[C:12]([CH:16]([OH:21])[C:17]([F:20])([F:18])[F:19])[N:11]([CH3:22])[C:10]=1[CH3:23]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 67282540HCID 67282540, compound

Product 1

HCID 67281686HCID 67281686, compoundYield 39.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A suspension of 3-benzyloxy-1,2-dimethyl-6-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-pyridin-4-one (190 mg, 0.58 mmol) and methanol (30 mL) was sonicated for a few min. The addition of a 6.00 N hydrochloric acid solution (50 μL, 0.30 mmol) gave a clear solution. To the solution was added Pd/C (10 wt. %, dry basis, on activated carbon, wet, Degussa type E101 NE/W, 80 mg). The debenzylation reaction was conducted under a hydrogen pressure of 50 psi. The reaction was completed within 30 min. A CELITE™ bed was prepared on a sintered glass, and washed with 6M HCl (100 mL), followed by water (7×50 mL) and then methanol (2×50 mL) under suction. The reaction mixture was filtered through the pre-treated CELITE™ bed. The pH of the filtrate was adjusted to 6 by addition of a solution of 6.00 N sodium hydroxide (ca. 50 μL), and then concentrated in vacuo. The first crop of the solid was collected by suction filtration and washed with deionized water thoroughly to give 3-hydroxy-1,2-dimethyl-6-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-pyridin-4-one (54 mg, 39% yield, HPLC Method 1 (Example 24), RT=9.4 min, HPLC purity (peak percent area): 95.8% at λ=280 nm). 1H NMR (CD3OD) δ ppm: 6.78 (s, 1H), 5.51 (q, J=6.5 Hz, 2H), 3.80 (s, 3H), 2.50 (s, 3H); MS-ESI (m/z) 238.2 [M+1]+, 169.2, 154.2 (100%), 140.1.

Workup

  1. customwas sonicated for a few min
  2. customgave a clear solution
  3. customThe debenzylation reaction
  4. customA CELITE™ bed was prepared on a sintered glass
  5. washwashed with 6M HCl (100 mL)
  6. filtrationThe reaction mixture was filtered through the pre-treated CELITE™ bed
  7. additionThe pH of the filtrate was adjusted to 6 by addition of a solution of 6.00 N sodium hydroxide (ca. 50 μL)
  8. concentrationconcentrated in vacuo
  9. filtrationThe first crop of the solid was collected by suction filtration
  10. washwashed with deionized water thoroughly

Sources & evidence

ORD record
ord-02c79e5d28eb45ee9790477c663d531b
Source dataset
uspto-grants-2011_09
Patent number
US08026261B2

Reaction notes

Loading…