HCID 71476986, compound → HCID 71477916, compound

HRID 1507003Notes

Reaction equation

HRID 1507003 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:34])([CH2:28][N:29]1[CH:33]=[N:32][N:31]=[N:30]1)[C:10]([F:27])([F:26])[C:11]1[CH:16]=[CH:15][C:14](/[CH:17]=[CH:18]/[CH2:19][O:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[CH:13][N:12]=1>CCO.[Pd]>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:34])([CH2:28][N:29]1[CH:33]=[N:32][N:31]=[N:30]1)[C:10]([F:27])([F:26])[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][CH2:19][O:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[CH:13][N:12]=1

Participants

4

Reactant 1

HCID 71476986HCID 71476986, compound

Product 1

HCID 71477916HCID 71477916, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

To a stirred solution of (E)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)-1-(5-(3-(2,2,2-trifluoroethoxy)prop-1-enyl)pyridin-2-yl)propan-2-ol (6; 140 mg, 0.28 mmol) in EtOH (10 mL) was added 10% Pd/C (14 mg), and the mixture was stirred under hydrogen atmosphere for 2 h. After consumption of the starting material (by TLC), the reaction mixture was filtered through a pad of Celite® and the Celite® cake was washed thoroughly with EtOAc (3×20 mL). The filtrate was concentrated under reduced pressure to obtain the crude material. Purification by silica gel column chromatography (eluting with 30% EtOAc/hexanes) afforded 45 (105 mg, 0.21 mmol, 75%) as a white solid. 1H NMR (500 MHz, CDCl3): δ 8.74 (s, 1H), 8.34 (s, 1H), 7.84 (s, 1H), 7.64 (d, J=6.5 Hz, 1H), 7.52 (d, J=8.0 Hz, 1H), 7.40-7.36 (m, 1H), 6.78-6.74 (m, 1H), 6.69-6.65 (m, 1H), 5.52 (d, J=14.0 Hz, 1H), 5.12 (d, J=14.0 Hz, 1H), 3.81 (q, J=8.0 Hz, 2H), 3.59 (t, J=6.0 Hz, 2H), 2.78 (t, J=8.0 Hz, 2H), 1.95-1.90 (m, 2H). MS (ESI): m/z 494 (M+H)+. HPLC: 96%

Workup

  1. customAfter consumption of the starting material (by TLC)
  2. filtrationthe reaction mixture was filtered through a pad of Celite®
  3. washthe Celite® cake was washed thoroughly with EtOAc (3×20 mL)
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customto obtain the crude material
  6. customPurification
  7. washby silica gel column chromatography (eluting with 30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-8aa96d4b1ddd469fa435cca427920326
Source dataset
uspto-grants-2015_12
Patent number
US09221791B2

Reaction notes

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