5-Benzyloxy-1-cyclopropyl-2-difluoromethyl-1H-pyridin-4-one → 1-Cyclopropyl-2-difluoromethyl-5-hydroxy-1H-pyridin-4-one

HRID 1187457Notes

Reaction equation

HRID 1187457 reaction equation
C([O:8][C:9]1[C:10](=[O:21])[CH:11]=[C:12]([CH:18]([F:20])[F:19])[N:13]([CH:15]2[CH2:17][CH2:16]2)[CH:14]=1)C1C=CC=CC=1.[H][H]>CO.[Pd]>[CH:15]1([N:13]2[CH:14]=[C:9]([OH:8])[C:10](=[O:21])[CH:11]=[C:12]2[CH:18]([F:20])[F:19])[CH2:16][CH2:17]1

Participants

5

Reactant 2

HCID 672822555-Benzyloxy-1-cyclopropyl-2-difluoromethyl-1H-pyridin-4-oneHCID 178418361HCID 178418361, compound

Product 1

HCID 250189091-Cyclopropyl-2-difluoromethyl-5-hydroxy-1H-pyridin-4-oneYield 77.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×

Procedure

A mixture of 5-benzyloxy-1-cyclopropyl-2-difluoromethyl-1H-pyridin-4-one (3.0 g, 10.3 mmol) and 10% Pd/C (340 mg) in methanol (60 mL) was subjected to hydrogenation in a Parr apparatus under a 15 psi hydrogen pressure for 22 min. The mixture was diluted with 300 mL of methanol, sonicated for 20 min, and then filtered through a pad of CELITE™ (pre-treated with HCl and washed to neutral with deionized water). The volume of the filtrate was reduced in vacuo until a solid precipitated out. The solid was collected by suction filtration. The recrystallization was repeated on the filtrate to obtain a second crop of solid. The combined solids were dried to constant weight in a vacuum oven thereby affording the title product (1.61 g) in 77% yield. HPLC purity (peak area percent) of product is 99.5% at λ=280 nm using HPLC Method 1 as described above. 1H NMR (400 MHz, DMSO-D6+D2O) δ (ppm): 7.54 (s, 1H), 7.33 (t, J=53.0 Hz, 1H, CF2H), 6.51 (s, 1H), 3.53-3.57 (m, 1H, N—CH), 1.07-1.10 (m, 4H, 2CH2); MS-ESI (m/z): 202.5 [M+1]+, 142.3 (100%); Anal. Calcd. for C9H9F2NO2: C, 53.73; H, 4.51; N, 6.96%. Found: C, 53.75; H, 4.80; N, 6.89%.

Workup

  1. customsonicated for 20 min
  2. filtrationfiltered through a pad of CELITE™ (pre-treated with HCl and washed to neutral with deionized water)
  3. customprecipitated out
  4. filtrationThe solid was collected by suction filtration
  5. customThe recrystallization
  6. customto obtain a second crop of solid
  7. customThe combined solids were dried to constant weight in a vacuum oven

Sources & evidence

ORD record
ord-01c656499d2a479391a5f68a2366034a
Source dataset
uspto-grants-2014_03
Patent number
US08673943B2

Reaction notes

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