HCID 71144475, compound → HCID 71143690, compound

HRID 1507005Notes

Reaction equation

HRID 1507005 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:30])([CH2:24][N:25]1[CH:29]=[N:28][N:27]=[N:26]1)[C:10]([C:13]1[N:18]=[CH:17][C:16](/[CH:19]=[CH:20]/[CH:21]([OH:23])[CH3:22])=[CH:15][CH:14]=1)([F:12])[F:11]>CO.[Pd]>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:30])([CH2:24][N:25]1[CH:29]=[N:28][N:27]=[N:26]1)[C:10]([C:13]1[N:18]=[CH:17][C:16]([CH2:19][CH2:20][CH:21]([OH:23])[CH3:22])=[CH:15][CH:14]=1)([F:12])[F:11]

Participants

4

Reactant 1

HCID 71144475HCID 71144475, compound

Product 1

HCID 71143690HCID 71143690, compoundYield 51.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of (E)-4-(6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(1H-tetrazol-1-yl)propyl)pyridin-3-yl)but-3-en-2-ol (46; 150 mg, 0.35 mmol) in CH3OH (10 mL) was added 10% Pd/C (10 mg), and the mixture was stirred under hydrogen atmosphere for 30 min. The reaction mixture was filtered through a pad of Celite®, the Celite® cake was washed with EtOAc (3×20 mL) and the filtrate was concentrated under reduced pressure. Purification by silica gel column chromatography (eluting with EtOAc/hexane) afforded 47 (77 mg, 0.18 mmol, 51%) as a viscous liquid. 1H NMR (500 MHz, CDCl3): δ 8.78 (s, 1H), 8.39-8.38 (m, 1H), 7.68-7.65 (m, 1H), 7.53-7.51 (m, 1H), 7.43-7.36 (m, 1H), 6.80-6.68 (m, 1H), 6.66-6.62 (m, 1H), 5.47-5.45 (m, 1H), 5.18-5.12 (m, 1H), 3.82-3.79 (m, 1H), 2.84-2.81 (m, 1H), 2.79-2.76 (m, 1H), 1.80-1.76 (m, 2H), 1.23 (d, J=7.0 Hz, 3H). MS (ESI): m/z 426 [M+H]+. HPLC: 98%.

Workup

  1. filtrationThe reaction mixture was filtered through a pad of Celite®
  2. washthe Celite® cake was washed with EtOAc (3×20 mL)
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customPurification
  5. washby silica gel column chromatography (eluting with EtOAc/hexane)

Sources & evidence

ORD record
ord-5342fc11658d4c7e84228a47beae861d
Source dataset
uspto-grants-2015_12
Patent number
US09221791B2

Reaction notes

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