Dichloromethane → Tert-butyl 5-cyclopropyl-2-fluoro-4-((4-oxocyclohexyl)oxy)benzoate

HRID 1849767Notes

Reaction equation

HRID 1849767 reaction equation
O1[C:5]2([CH2:10][CH2:9][CH:8]([O:11][C:12]3[C:24]([CH:25]4[CH2:27][CH2:26]4)=[CH:23][C:15]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[C:14]([F:28])[CH:13]=3)[CH2:7][CH2:6]2)[O:4]CC1.FC(F)(F)C(O)=O.ClCCl>O1CCCC1.O>[CH:25]1([C:24]2[C:12]([O:11][CH:8]3[CH2:7][CH2:6][C:5](=[O:4])[CH2:10][CH2:9]3)=[CH:13][C:14]([F:28])=[C:15]([CH:23]=2)[C:16]([O:18][C:19]([CH3:21])([CH3:22])[CH3:20])=[O:17])[CH2:27][CH2:26]1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 86703650Tert-butyl 4-(1,4-dioxaspiro[4.5]decan-8-yloxy)-5-cyclopropyl-2-fluorobenzoate

Product 1

HCID 86703651Tert-butyl 5-cyclopropyl-2-fluoro-4-((4-oxocyclohexyl)oxy)benzoateYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of tert-butyl 4-(1,4-dioxaspiro[4.5]decan-8-yloxy)-5-cyclopropyl-2-fluorobenzoate (0.557 g, 1.44 mmol) in tetrahydrofuran (1.5 mL) and water (1.5 mL) was added trifluoroacetic acid (0.5 mL) and the reaction mixture was stirred for 16 hours at ambient temperature. After addition of dichloromethane (100 mL), the mixture was washed with saturated sodium bicarbonate solution (10 mL), brine (10 mL), and dried over anhydrous sodium sulfate. Filtration and concentration of the filtrate in vacuo gave a residue which was purified by silica gel column chromatography using 0-30% ethyl acetate in hexanes as eluent to afford the title compound as a colorless oil (0.300 g, 60%): 1H NMR (300 MHz, CDCl3) δ 7.42 (d, J=8.4 Hz, 1H), 6.59 (d, J=12.6 Hz, 1H), 4.80-4.71 (m, 1H), 2.77-2.62 (m, 2H), 2.42-2.27 (m, 4H), 2.14-1.93 (m, 3H), 1.56 (s, 9H), 0.94-0.84 (m, 2H), 0.65-0.60 (m, 2H).

Workup

  1. washthe mixture was washed with saturated sodium bicarbonate solution (10 mL), brine (10 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationFiltration and concentration of the filtrate in vacuo
  4. customgave a residue which
  5. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0173cdbf2fc74081a10b80924b21b459
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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