Triethylsilane → HCID 71476161, compound

HRID 1396226Notes

Reaction equation

HRID 1396226 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:37])([CH2:31][N:32]1[CH:36]=[N:35][N:34]=[N:33]1)[C:10]([F:30])([F:29])[C:11]1[CH:16]=[CH:15][C:14]([CH:17](O)[C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=2)=[CH:13][N:12]=1.C([SiH](CC)CC)C>CCO.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:37])([CH2:31][N:32]1[CH:36]=[N:35][N:34]=[N:33]1)[C:10]([F:30])([F:29])[C:11]1[CH:16]=[CH:15][C:14]([CH2:17][C:18]2[CH:19]=[CH:20][C:21]([C:24]([F:27])([F:25])[F:26])=[CH:22][CH:23]=2)=[CH:13][N:12]=1

Participants

5

Reactant 2

HCID 12052TriethylsilaneHCID 71476160HCID 71476160, compound

Product 1

HCID 71476161HCID 71476161, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolvent

Procedure

To a stirred solution of 2-(2,4-difluorophenyl)-1,1-difluoro-1-(5-(hydroxy(4-(trifluoromethyl)phenyl)methyl)pyridin-2-yl)-3-(1H-tetrazol-1-yl)propan-2-ol (72; 100 mg, 0.19 mmol) in EtOH (5 mL) was added triethylsilane (˜0.18 mL, 1.13 mmol) and Pd(OAc)2 (20 mg, 0.02 mmol) at RT under inert atmosphere. The reaction mixture was stirred under reflux conditions for 7-8 h; progress of the reaction was monitored by TLC. The reaction mixture was allowed to cool to RT, filtered through a pad of Celite®, and the Celite® cake was washed with EtOH (3×25 mL). The filtrate was concentrated under reduced pressure to obtain the crude material. Purification by silica gel column chromatography (eluting with 40% EtOAc/hexanes) afforded 73 (30 mg, 0.058 mmol, 31%) as an off-white solid. 1H NMR (500 MHz, CDCl3): δ 8.73 (s, 1H), 8.35 (s, 1H), 7.63-7.52 (m, 5H), 7.40-7.35 (m, 1H), 7.25-7.23 (m, 1H), 6.78-6.74 (m, 1H), 6.69-6.66 (m, 1H), 5.50 (d, J=14.5 Hz, 1H), 5.14 (d, J=14.5 Hz, 1H), 4.08 (s, 2H). MS (ESI): m/z 512 [M+H]+. HPLC: 91.7%.

Workup

  1. filtrationfiltered through a pad of Celite®
  2. washthe Celite® cake was washed with EtOH (3×25 mL)
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customto obtain the crude material
  5. customPurification
  6. washby silica gel column chromatography (eluting with 40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-c20806f5e9be418fa846308d5913aa9a
Source dataset
uspto-grants-2014_12
Patent number
US08901121B2

Reaction notes

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