HCID 71143696, compound → HCID 71143730, compound

HRID 1396222Notes

Reaction equation

HRID 1396222 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:32])([CH2:26][N:27]1[CH:31]=[N:30][N:29]=[N:28]1)[C:10]([F:25])([F:24])[C:11]1[CH:16]=[CH:15][C:14](/[CH:17]=[CH:18]/[CH2:19][O:20][CH:21]([CH3:23])[CH3:22])=[CH:13][N:12]=1>CO.[Pd]>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:32])([CH2:26][N:27]1[CH:31]=[N:30][N:29]=[N:28]1)[C:10]([F:25])([F:24])[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][CH2:19][O:20][CH:21]([CH3:23])[CH3:22])=[CH:13][N:12]=1

Participants

4

Reactant 1

HCID 71143696HCID 71143696, compound

Product 1

HCID 71143730HCID 71143730, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a stirred solution of (E)-2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(3-isopropoxyprop-1-en-1-yl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (54; 24 mg, 0.05 mmol) in CH3OH (2 mL) was added 10% Pd/C (2 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 (3×10 mL). The filtrate was concentrated under reduced pressure to obtain the crude material. Purification by silica gel column chromatography (eluting with 30% EtOAc/hexane) afforded 55 (20 mg, 0.04 mmol, 80%) as a colorless semi-solid. 1H NMR (500 MHz, CDCl3): δ 8.74 (s, 1H), 8.36 (s, 1H), 7.89 (s, 1H), 7.64 (d, J=8.0 Hz, 1H), 7.50 (d, J=8.0 Hz, 1H), 7.36-7.31 (m, 1H), 6.77-6.73 (m, 1H), 6.67-6.63 (m, 1H), 5.56 (d, J=14.0 Hz, 1H), 5.09 (d, J=14.0 Hz, 1H), 3.53 (q, J=6.0 Hz, 1H), 3.38 (t, J=6.0 Hz, 2H), 2.75 (t, J=8.0 Hz, 2H), 1.86 (q, J=6.0 Hz, 2H), 1.14 (d, J=6.0 Hz, 6H). MS (ESI): m/z 454 (M+H)+. HPLC: 93%.

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 (3×10 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/hexane)

Sources & evidence

ORD record
ord-fe39b6dd9dc64b7dbdc8e7c3e1f87895
Source dataset
uspto-grants-2014_12
Patent number
US08901121B2

Reaction notes

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