HCID 67281584, compound → HCID 67282784, compound

HRID 1187487Notes

Reaction equation

HRID 1187487 reaction equation
C([O:8][C:9]1[C:10](=[O:22])[CH:11]=[C:12]([CH:16]([OH:21])[C:17]([F:20])([F:19])[F:18])[N:13]([CH3:15])[CH:14]=1)C1C=CC=CC=1>CO.[Pd]>[OH:8][C:9]1[C:10](=[O:22])[CH:11]=[C:12]([CH:16]([OH:21])[C:17]([F:18])([F:19])[F:20])[N:13]([CH3:15])[CH:14]=1

Participants

4

Reactant 1

HCID 67281584HCID 67281584, compound

Product 1

HCID 67282784HCID 67282784, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×

Procedure

A mixture of 5-benzyloxy-1-methyl-2-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-pyridin-4-one (3.1 g, 9.9 mmol) and methanol (60 mL) was sonicated to give a clear solution. To the solution was added Pd/C (10 wt. %, dry basis, on activated carbon, wet, Degussa type E101 NE/W, 0.58 g). The debenzylation reaction was conducted in a Parr hydrogenator under an atmosphere of hydrogen pressurized to 50 psi. The reaction was completed within 20 min. The reaction mixture was diluted with MeOH (100 mL), sonicated for about 20 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 filtrate was collected and concentrated in vacuo to give 5-hydroxy-1-methyl-2-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-pyridin-4-one as a solid product (2.05 g, 92% yield, HPLC Method 1 (Example 24), RT=7.4 min, HPLC purity (peak percent area): 99.4% at λ=280 nm). 1H NMR (DMSO-d6+D2O) δ ppm: 7.50 (s, 1H), 6.50 (s, 1H), 5.37 (q, J=6.5 Hz, 1H), 3.67 (s, 3H); MS-ESI (m/z) 224.2 [M+1]+, 206.2, 155.2 (100%), 140.1, 126.1.

Workup

  1. customwas sonicated
  2. customto give a clear solution
  3. customThe debenzylation reaction
  4. customsonicated for about 20 min
  5. customA CELITE™ bed was prepared on a sintered glass
  6. washwashed with 6M HCl (100 mL)
  7. filtrationThe reaction mixture was filtered through the pre-treated CELITE™ bed
  8. customThe filtrate was collected
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-480a6393d46648dc8e442fce9f2901e3
Source dataset
uspto-grants-2014_03
Patent number
US08673943B2

Reaction notes

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