Dimethylformamide → HCID 21070519, compound

HRID 1371730Notes

Reaction equation

HRID 1371730 reaction equation
[C:1]([Si:5]([O:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([F:16])=[CH:11][C:10]=1[O:17][CH3:18])([CH3:7])[CH3:6])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.CN(C)[CH:26]=[O:27].[Cl-].[NH4+]>O1CCCC1.O>[C:1]([Si:5]([CH3:7])([CH3:6])[O:8][C:9]1[C:10]([O:17][CH3:18])=[C:11]([C:12]([F:16])=[C:13]([F:15])[CH:14]=1)[CH:26]=[O:27])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 21070650HCID 21070650, compoundHCID 178418339Butyllithium

Product 1

HCID 21070519HCID 21070519, compoundYield 69.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of tert-butyl-(4,5-difluoro-2-methoxy-phenoxy)-dimethyl-silane (5.2 g, 18.95 mmol) in tetrahydrofuran (60 mL) cooled to −78° C. was added n-butyllithium (9.096 mL, 22.74 mmol) dropwise over a period of 15 minutes. At the end of the addition, the reaction mixture was stirred at −78° C. for 1 hour. Dimethylformamide (1.737 mL, 22.74 mmol) was added and the reaction mixture was stirred at −78° C. for 2 hours. Saturated solution of ammonium chloride (˜5 mL) was added, and then the mixture was diluted with 100 mL of water. The aqueous layer was extracted with ethyl acetate (2×75 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 4% ethyl acetate in hexanes) yielded 3-(tert-butyl-dimethyl-silanyloxy)-5,6-difluoro-2-methoxy-benzaldehyde as clear oil (3.96 g, 69%). LR-MS (M+) 302.2.

Workup

  1. additionAt the end of the addition
  2. stirringthe reaction mixture was stirred at −78° C. for 2 hours
  3. extractionThe aqueous layer was extracted with ethyl acetate (2×75 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationThe solids were filtered off
  7. concentrationthe filtrate was concentrated in vacuo
  8. customPurification of the crude residue
  9. washby flash chromatography (Biotage system, 60 Å silica gel, eluting with 4% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-c35a1ea35650495b8daa07ee56b76318
Source dataset
uspto-grants-2007_01
Patent number
US07157455B2

Reaction notes

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