Sodium Hydroxide → N-(2-{[tert-Butyl(dimethyl)silyl]oxy}ethyl)-3-chloro-2,4-difluoro-N-methylbenzamide

HRID 548666Notes

Reaction equation

HRID 548666 reaction equation
[Cl:1][C:2]1[C:3]([F:12])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5](Cl)=[O:6].[Si:13]([O:20][CH2:21][CH2:22][NH:23][CH3:24])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].[OH-].[Na+]>C(Cl)Cl>[Si:13]([O:20][CH2:21][CH2:22][N:23]([CH3:24])[C:5](=[O:6])[C:4]1[CH:8]=[CH:9][C:10]([F:11])=[C:2]([Cl:1])[C:3]=1[F:12])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:14])[CH3:15]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 27735383-Chloro-2,4-difluorobenzoyl chlorideHCID 16203640N-(2-(tert-Butyldimethylsilyloxy)ethyl)methylamine

Product 1

HCID 57663164N-(2-{[tert-Butyl(dimethyl)silyl]oxy}ethyl)-3-chloro-2,4-difluoro-N-methylbenzamideYield 68.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-Chloro-2,4-difluorobenzoyl chloride (1.92 g, 9.1 mmol) was added slowly to a stirred solution of (2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)methylamine (1.89 g, 10.0 mmol) in a 1:1 mixture of 10% sodium hydroxide solution and DCM at 0° C. The reaction mixture was then allowed to warm up to RT and left to stir for 5 hours. The phases were separated and the aqueous phase was extracted with DCM (3×50 mL). The combined extracts were dried (MgSO4), filtered and evaporated to give a pale yellow oil. Purification by column chromatography on silica, eluting with 0-50% ethyl acetate in hexanes, gave the title compound as a colourless oil (2.26 g) 1H NMR δ (CDCl3): 0.00 (s, 6H), 0.82 (s, 9H), 2.93 (s, 3H), 3.58 (t, 2H), 3.81 (t, 2H), 6.95 (dtd, 1H), 7.16-7.22 (m, 1H)

Workup

  1. waitleft
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with DCM (3×50 mL)
  4. dry with materialThe combined extracts were dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customto give a pale yellow oil
  8. customPurification by column chromatography on silica
  9. washeluting with 0-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-94da99158db84acbb060cf863558156e
Source dataset
uspto-grants-2011_05
Patent number
US07943607B2

Reaction notes

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