Imidazole → HCID 67053743, compound

HRID 1845113Notes

Reaction equation

HRID 1845113 reaction equation
[F:1][CH:2]([F:13])[C:3]1[N:8]=[CH:7][C:6]([C@@H:9]([OH:12])[CH2:10][OH:11])=[CH:5][CH:4]=1.[Si:14](Cl)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15].N1C=CN=C1.O>C(Cl)Cl>[Si:14]([O:11][CH2:10][C@@H:9]([C:6]1[CH:7]=[N:8][C:3]([CH:2]([F:1])[F:13])=[CH:4][CH:5]=1)[OH:12])([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 28928tert-Butyldimethylsilyl chlorideHCID 58188067HCID 58188067, compound

Product 1

HCID 67053743HCID 67053743, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (R)-1-(6-(difluoromethyl)pyridin-3-yl)ethane-1,2-diol (2.5 g, 13.2 mmol) in dry CH2Cl2 at room temperature were added tert-butyldimethylsilyl chloride (2.19 g, 14.5 mmol) and imidazole (0.99 g, 14.5 mmol). The resulting reaction mixture was stirred for 16 h. After completion of the reaction, the reaction mixture was treated with water and extracted with CH2Cl2. The organic layer was dried over anhydrous Na2SO4 and the solvents were evaporated in vacuo. The residue was purified by column chromatography (SiO2, 20% EtOAc/pet. ether) to afford the title compound (3g, 75% yield). MS: 304 [M+1]+; 1H-NMR (300 MHz, CDCl3): 8.63 (s, 1H), 7.89 (d, 1H, J=8.2 Hz), 7.63 (d, 1H, J=8.2 Hz), 6.64 (t, 1H, J=55.4 Hz), 4.82-4.86 (m, 1H), 3.82 (dd, 1H, J=10.1, 3.7 Hz), 3.58 (dd, 1H, J=10.1, 7.8 Hz), 0.9 (s, 9H), 0.06 (s, 6H).

Workup

  1. customThe resulting reaction mixture
  2. customAfter completion of the reaction
  3. extractionextracted with CH2Cl2
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. customthe solvents were evaporated in vacuo
  6. customThe residue was purified by column chromatography (SiO2, 20% EtOAc/pet. ether)

Sources & evidence

ORD record
ord-e639bbcd38094941a563299f2a1e51b2
Source dataset
uspto-grants-2015_02
Patent number
US08946439B2

Reaction notes

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