Trifluoroacetic acid → Tert-butyl 5-cyclopropyl-2-fluoro-4-((4-oxocyclohexyl)methoxy)benzoate

HRID 1849740Notes

Reaction equation

HRID 1849740 reaction equation
O1[C:5]2([CH2:10][CH2:9][CH:8]([CH2:11][O:12][C:13]3[C:25]([CH:26]4[CH2:28][CH2:27]4)=[CH:24][C:16]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[C:15]([F:29])[CH:14]=3)[CH2:7][CH2:6]2)[O:4]CC1.FC(F)(F)C(O)=O>O1CCCC1.O.C(OCC)(=O)C>[CH:26]1([C:25]2[C:13]([O:12][CH2:11][CH:8]3[CH2:7][CH2:6][C:5](=[O:4])[CH2:10][CH2:9]3)=[CH:14][C:15]([F:29])=[C:16]([CH:24]=2)[C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[CH2:28][CH2:27]1

Participants

6

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86703618Tert-butyl 4-(1,4-dioxaspiro[4.5]decan-8-ylmethoxy)-5-cyclopropyl-2-fluorobenzoate

Product 1

HCID 86703619Tert-butyl 5-cyclopropyl-2-fluoro-4-((4-oxocyclohexyl)methoxy)benzoateYield 96%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of tert-butyl 4-(1,4-dioxaspiro[4.5]decan-8-ylmethoxy)-5-cyclopropyl-2-fluorobenzoate (3.16 g, 7.77 mmol) in tetrahydrofuran (10 mL) and water (10 mL) was added trifluoroacetic acid (2.7 mL) and the reaction mixture was stirred for 16 hours at ambient temperature. After diluting the reaction mixture with ethyl acetate (200 mL), the organic phase was washed with 1 N sodium hydroxide solution (2×15 mL), brine (15 mL), and dried over anhydrous sodium sulfate. Filtration and concentration of the filtrate under reduced pressure gave a residue which was purified by silica gel column chromatography using 0-40% ethyl acetate in hexanes as eluent to afford the title compound as a colorless oil (2.70 g, 96%): 1H NMR (300 MHz, CDCl3) δ 7.37 (d, J=8.4 Hz, 1H), 6.50 (d, J=12.5 Hz, 1H), 3.90 (d, J=6.0 Hz, 2H), 2.53-2.15 (m, 8H), 2.03-1.92 (m, 1H), 1.73-1.59 (m, 1H), 1.55 (s, 9H), 0.92-0.83 (m, 2H), 0.65-0.58 (m, 2H).

Workup

  1. washthe organic phase was washed with 1 N sodium hydroxide solution (2×15 mL), brine (15 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationFiltration and concentration of the filtrate under reduced pressure
  4. customgave a residue which
  5. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-44d39c488120480db7dd616f5c74d0d6
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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