(Trifluoromethyl)trimethylsilane → Ethyl 2-methyl-2-[4-(2-{[5-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-2-yl][4-(trifluoromethoxy)benzyl]amino}ethyl)phenoxy]propanoate

HRID 2251537Notes

Reaction equation

HRID 2251537 reaction equation
[CH:1]([C:3]1[CH:4]=[CH:5][C:6]([N:9]([CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[CH:30][CH:29]=2)[CH2:10][CH2:11][C:12]2[CH:26]=[CH:25][C:15]([O:16][C:17]([CH3:24])([CH3:23])[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:14][CH:13]=2)=[N:7][CH:8]=1)=[O:2].[F:39][C:40]([Si](C)(C)C)([F:42])[F:41].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[CH3:24][C:17]([O:16][C:15]1[CH:25]=[CH:26][C:12]([CH2:11][CH2:10][N:9]([C:6]2[CH:5]=[CH:4][C:3]([CH:1]([OH:2])[C:40]([F:42])([F:41])[F:39])=[CH:8][N:7]=2)[CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[CH:30][CH:29]=2)=[CH:13][CH:14]=1)([CH3:23])[C:18]([O:20][CH2:21][CH3:22])=[O:19]

Participants

5

Reactant 3

HCID 552549(Trifluoromethyl)trimethylsilane2×HCID 2724141Tetrabutylammonium Fluoride2×HCID 59643273Ethyl 2-[4-(2-{(5-formylpyridin-2-yl)[4-(trifluoromethoxy)benzyl]amino}ethyl)phenoxy]-2-methylpropanoate

Product 1

HCID 86598931Ethyl 2-methyl-2-[4-(2-{[5-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-2-yl][4-(trifluoromethoxy)benzyl]amino}ethyl)phenoxy]propanoateYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of ethyl 2-[4-(2-{(5-formylpyridin-2-yl)[4-(trifluoromethoxy)benzyl]amino}ethyl)phenoxy]-2-methylpropanoate (400 mg; 0.75 mmol) in 5 ml of dry THF was treated in an ice bath, under nitrogen, with trifluoromethyltrimethylsilane (128 mg; 0.90 mmol), followed by tetrabutylammonium fluoride (0.075 ml of a 1M solution in THF; 0.075 mmol). The reaction mixture was allowed to warm to rt and stirred overnight. Additional trifluoromethyltrimethylsilane (128 mg; 0.90 mmol) and tetrabutylammonium fluoride (0.075 ml) were added. After 6 hours the previous reagents were added again in the same amounts. After stirring at rt overnight, the reaction mixture was partitioned between ethyl acetate and water. The organic phase was washed with water and brine, dried over sodium sulfate and concentrated. Purification by radial chromatography using ethyl acetate-hexane mixtures (5–40% gradient) afforded ethyl 2-methyl-2-[4-(2-{[5-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-2-yl][4-(trifluoromethoxy)benzyl]amino}ethyl)phenoxy]propanoate (247 mg; 55% yield).

Workup

  1. additionAfter 6 hours the previous reagents were added again in the same amounts
  2. stirringAfter stirring at rt overnight
  3. customthe reaction mixture was partitioned between ethyl acetate and water
  4. washThe organic phase was washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customPurification by radial chromatography

Sources & evidence

ORD record
ord-450e99f3057b4dda9700521a12636f45
Source dataset
uspto-grants-2008_01
Patent number
US07319104B2

Reaction notes

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