1,4-Dioxaspiro(4.5)decan-8-ol → Tert-butyl 4-(1,4-dioxaspiro[4.5]decan-8-yloxy)-5-chloro-2-fluorobenzoate

HRID 1849765Notes

Reaction equation

HRID 1849765 reaction equation
[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[Cl:12][C:13]1[C:14](F)=[CH:15][C:16]([F:26])=[C:17]([CH:25]=1)[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].CC(C)([O-])C.[K+]>CS(C)=O>[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([O:11][C:14]3[C:13]([Cl:12])=[CH:25][C:17]([C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])=[C:16]([F:26])[CH:15]=3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 5673521,4-Dioxaspiro(4.5)decan-8-olHCID 23665647Potassium tert-butoxideHCID 58042499tert-butyl 5-chloro-2,4-difluorobenzoate

Product 1

HCID 86703649Tert-butyl 4-(1,4-dioxaspiro[4.5]decan-8-yloxy)-5-chloro-2-fluorobenzoateYield 12.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a mixture of 1,4-dioxaspiro[4.5]decan-8-ol (2.40 g, 15.20 mmol) and tert-butyl 5-chloro-2,4-difluorobenzoate (3.78 g, 15.20 mmol) in anhydrous dimethyl sulfoxide was added potassium tert-butoxide (2.56 g, 22.80 mmol) and the reaction mixture was stirred for 16 hours at ambient temperature. After dilution with ethyl acetate (200 mL), the organic phase was washed with water (3×10 mL), brine (10 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 0-30% ethyl acetate in hexanes as eluent to afford the title compound as a colorless oil (0.709 g, 12%): 1H NMR (300 MHz, CDCl3) δ 7.85 (d, J=7.8 Hz, 1H), 6.64 (d, J=12.3 Hz, 1H), 4.53-4.46 (m, 1H), 3.97-3.92 (m, 4H), 2.04-1.58 (m, 8H), 1.55 (d, J=1.0 Hz, 9H).

Workup

  1. washAfter dilution with ethyl acetate (200 mL), the organic phase was washed with water (3×10 mL), brine (10 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-89ae82330eb14f6aae44f965e060c6e0
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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