Water → HCID 67277501, compound

HRID 1694789Notes

Reaction equation

HRID 1694789 reaction equation
[CH3:1][N:2]([CH3:27])[S:3]([N:6]1[CH:10]=[C:9]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[C:13]=2[F:19])[N:8]=[C:7]1[Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])(=[O:5])=[O:4].[CH:28]([N-]C(C)C)(C)C.[Li+].CI.O>O1CCCC1>[CH3:27][N:2]([CH3:1])[S:3]([N:6]1[CH:10]=[C:9]([CH:11]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[C:13]=2[F:19])[CH3:28])[N:8]=[C:7]1[Si:20]([C:23]([CH3:24])([CH3:26])[CH3:25])([CH3:21])[CH3:22])(=[O:5])=[O:4]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 58951924HCID 58951924, compound

Product 1

HCID 67277501HCID 67277501, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-75 °C

Procedure

An amount of 2.9 g (7.0 mmol) of 2-(tert-butyl-dimethyl-silanyl)-4-(2,3-difluoro-benzyl)-imidazole-1-sulfonic acid dimethylamide was dissolved in 30 ml tetrahydrofuran and added drop-wise to a freshly prepared solution of lithium diisopropylamide in tetrahydrofuran (from 6.54 ml 1.6M BuLi and 1.06 g diisopropylamine). After stirring for 1 h at −75° C., 1.14 g (8.0 mmol) methyl iodide was added, and stirring was continued overnight at ambient temperature. Water was added to quench the reaction. The aqueous phase was extracted with ethyl acetate (3 times) and the combined organic extracts were dried over MgSO4, filtered and concentrated. The residue was purified by flash chromatography (silica gel, hexanes/ethyl acetate 4:1) to yield 2.47 g of rac-2-(tert-butyl-dimethyl-silanyl)-4-[1-(2,3-difluoro-phenyl)-ethyl]-imidazole-1-sulfonic acid dimethylamide (MS (ISP): 430.3 ((M+H)+.), light yellow oil). This material was separated by chiral column chromatography (Chiral OD, isopropanol/heptane=2:98) to yield 0.785 g (26%) of (+)-2-(tert-butyl-dimethyl-silanyl)-4-[1-(2,3-difluoro-phenyl)-ethyl]-imidazole-1-sulfonic acid dimethylamide and 0.946 g (32%) of (+)-2-(tert-butyl-dimethyl-silanyl)-4-[1-(2,3-difluoro-phenyl)-ethyl]-imidazole-1-sulfonic acid dimethylamide.

Workup

  1. stirringstirring
  2. waitwas continued overnight at ambient temperature
  3. customto quench
  4. customthe reaction
  5. extractionThe aqueous phase was extracted with ethyl acetate (3 times)
  6. dry with materialthe combined organic extracts were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography (silica gel, hexanes/ethyl acetate 4:1)

Sources & evidence

ORD record
ord-8a8c20432caa410994ab1c3e4c029316
Source dataset
uspto-grants-2012_04
Patent number
US08158668B2

Reaction notes

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