Tetrabutylammonium Fluoride → HCID 11546336, compound

HRID 2038601Notes

Reaction equation

HRID 2038601 reaction equation
[F:1][C:2]1[C:3]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]#[C:29][Si](C)(C)C)=[CH:24][C:23]=2[F:34])=[C:4]([CH:12]=[C:13]([CH2:16][O:17][CH2:18][CH2:19][OH:20])[C:14]=1[F:15])[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[C:28]([C:25]1[CH:26]=[CH:27][C:22]([NH:21][C:3]2[C:2]([F:1])=[C:14]([F:15])[C:13]([CH2:16][O:17][CH2:18][CH2:19][OH:20])=[CH:12][C:4]=2[C:5]([NH:7][O:8][CH2:9][CH2:10][OH:11])=[O:6])=[C:23]([F:34])[CH:24]=1)#[CH:29]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86634351HCID 86634351, compound

Product 1

HCID 11546336HCID 11546336, compoundYield 68.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the resultant 3,4-difluoro-2-(2-fluoro-4-trimethylsilanylethynyl-phenylamino)-N-(2-hydroxy-ethoxy)-5-(2-hydroxy-ethoxymethyl)-benzamide (37.6 mg) in tetrahydrofuran (anhydrous, 1.0 ml) was added tetra-n-butylammonium fluoride (1 M solution in THF, 113 μL, 113 μmol) at room temperature, and the mixture was stirred for 3 hours. The reaction mixture was concentrated under reduced pressure. 0.1 N Hydrochloric acid was added to the resultant residue, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with 0.1 N hydrochloric acid and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (Presep Silica Gel Type S (Wako Pure Chemical Industries), 10 g, CH2Cl2/MeOH (10:1 to 5:1)) to give 2-(4-ethynyl-2-fluoro-phenylamino)-3,4-difluoro-N-(2-hydroxy-ethoxy)-5-(2-hydroxy-ethoxymethyl)-benzamide (21.9 mg, 68%) as a yellow powder.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. addition0.1 N Hydrochloric acid was added to the resultant residue
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe combined organic layers were washed with 0.1 N hydrochloric acid and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resultant residue was purified by silica gel column chromatography (Presep Silica Gel Type S (Wako Pure Chemical Industries), 10 g, CH2Cl2/MeOH (10:1 to 5:1))

Sources & evidence

ORD record
ord-8a122bb4fcab4e66845b8323815e955e
Source dataset
uspto-grants-2013_11
Patent number
US08575391B2

Reaction notes

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