Water → (S)-2,2,2-trifluoro-N-(6-methoxy-3-methylene-2,3-dihydro-1H-inden-1-yl)-acetamide

HRID 501707

Reaction equation

HRID 501707 reaction equation
[CH3:1]C(C)([O-])C.[K+].[F:7][C:8]([F:25])([F:24])[C:9]([NH:11][C@@H:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=2)[C:14](=O)[CH2:13]1)=[O:10].O>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[F:7][C:8]([F:25])([F:24])[C:9]([NH:11][C@@H:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([O:21][CH3:22])[CH:19]=2)[C:14](=[CH2:1])[CH2:13]1)=[O:10]

Participants

6

Reactant 3

HCID 962WaterHCID 1472787(S)-2,2,2-trifluoro-N-(6-methoxy-3-oxo-2,3-dihydro-1H-inden-1-yl)acetamideHCID 23665647Potassium tert-butoxide

Product 1

HCID 86622338(S)-2,2,2-trifluoro-N-(6-methoxy-3-methylene-2,3-dihydro-1H-inden-1-yl)-acetamideYield 92.7%

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Step AF (2): To a solution of methyltriphenylphosphonium bromide (1.6 g) in THF (5 mL) was added potassium t-butoxide (700 mg), and the mixture was stirred at rt for 30 min to form a deep yellow solution. A solution of (S)-2,2,2-trifluoro-N-(6-methoxy-3-oxo-2,3-dihydro-1H-inden-1-yl)acetamide (500 mg) in THF (2 mL) was added, and the reaction was continued for 40 min. Water was added, the aqueous layer was extracted with EtOAc (×3), and the combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was evaporated in vacuo, and the residue was purified by Biotage chromatography eluting with 1-10% EtOAc/hexanes to give (S)-2,2,2-trifluoro-N-(6-methoxy-3-methylene-2,3-dihydro-1H-inden-1-yl)-acetamide as a white solid (460 mg). 1H NMR (400 MHz, CDCl3) δ 7.45 (1H, d), 6.91 (1H, dd), 6.83 (1H, d), 6.45 (1H, br. S), 5.38 (1H, dt), 5.38 (1H, t), 4.99 (1H, t), 3.81 (3H, s), 3.45 (1H, m), and 2.62 (1H, m).

Workup

  1. customto form a deep yellow solution
  2. waitthe reaction was continued for 40 min
  3. extractionthe aqueous layer was extracted with EtOAc (×3)
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. customThe filtrate was evaporated in vacuo
  8. customthe residue was purified by Biotage chromatography
  9. washeluting with 1-10% EtOAc/hexanes

Sources & evidence

ORD record
ord-80f83f9a40084def86405aa8dd3ec3ad
Source dataset
uspto-grants-2010_08
Patent number
US07772221B2

Linked notes

Loading…