2-Dimethylaminopyridine → HCID 21070650, compound

HRID 1435308Notes

Reaction equation

HRID 1435308 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([OH:9])=[C:4]([O:10][CH3:11])[CH:3]=1.C(N(CC)C(C)C)(C)C.[Si:21](Cl)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22].CN(C1C=CC=CN=1)C>C(Cl)Cl>[C:24]([Si:21]([O:9][C:5]1[CH:6]=[C:7]([F:8])[C:2]([F:1])=[CH:3][C:4]=1[O:10][CH3:11])([CH3:23])[CH3:22])([CH3:27])([CH3:26])[CH3:25]

Participants

6

Reactant 4

HCID 218852-DimethylaminopyridineHCID 28928tert-Butyldimethylsilyl chlorideHCID 81531DiisopropylethylamineHCID 18687664HCID 18687664, compound

Product 1

HCID 21070650HCID 21070650, compoundYield 81.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4,5-difluoro-2-methoxy-phenol (3.75 g, 23.42 mmol, Example 264) in methylene chloride (60 mL) cooled to 0° C. were added N,N-diisopropylethylamine (4.895 mL, 28.10 mmol), tert-butyldimethylsilyl chloride (4.367 g, 28.10 mmol, Aldrich), and dimethylaminopyridine (286 mg, 2.342 mmol, Aldrich). At the end of addition, the ice bath was removed and the reaction mixture was stirred at room temperature for 90 minutes. Water (30 mL) was added and the layers were separated. The aqueous layer was extracted with methylene chloride (20 mL). The combined organic layers were washed with brine and dried over anhydrous magnesium sulfate. The solids were filtered off and the filtrate was concentrated in vacuo. Purification of the crude residue by flash chromatography (Biotage system, 60 Å silica gel, eluting with 3% ethyl acetate in hexanes) yielded tert-butyl-(4,5-difluoro-2-methoxy-phenoxy)-dimethyl-silane as a clear oil (5.22 g, 81%).

Workup

  1. additionAt the end of addition
  2. customthe ice bath was removed
  3. additionWater (30 mL) was added
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with methylene chloride (20 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationThe solids were filtered off
  9. concentrationthe filtrate was concentrated in vacuo
  10. customPurification of the crude residue
  11. washby flash chromatography (Biotage system, 60 Å silica gel, eluting with 3% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-d0225769a97c42fd99fd692af62fc3ed
Source dataset
uspto-grants-2009_11
Patent number
US07615634B2

Reaction notes

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