Ethyl Acetate → Tert-butyl 4-(1,4-dioxaspiro[4.5]decan-8-ylmethoxy)-5-chloro-2-fluorobenzoate

HRID 1849738Notes

Reaction equation

[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([CH2:11][OH:12])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[Cl:13][C:14]1[C:15](F)=[CH:16][C:17]([F:27])=[C:18]([CH:26]=1)[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>CS(C)=O>[O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([CH2:11][O:12][C:15]3[C:14]([Cl:13])=[CH:26][C:18]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])=[C:17]([F:27])[CH:16]=3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1

Participants

Conditions

Temperature: 75 °C

Procedure

To a mixture of 1,4-dioxaspiro[4.5]decan-8-ylmethanol (5.00 g, 29.0 mmol) and tert-butyl 5-chloro-2,4-difluorobenzoate (7.22 g, 29.00 mmol) in anhydrous dimethyl sulfoxide (30 mL) was added cesium carbonate (18.90 g, 58.00 mmol) and the reaction mixture was heated at 70-80° C. for 4 hours. After cooling to ambient temperature, ethyl acetate was added (200 mL) and the mixture was washed with water (4×15 mL), brine (2×15 mL); dried over anhydrous sodium sulfate, and filtered. After concentration of the filtrate in vacuo, the residue 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 (5.06 g, 44%): 1H NMR (300 MHz, CDCl3) 7.85 (d, J=7.7 Hz, 1H), 6.60 (d, J=12.2 Hz, 1H), 3.95-3.93 (m, 4H), 3.83 (d, J=6.3 Hz, 2H), 1.98-1.87 (m, 4H), 1.84-1.71 (m, 4H), 1.64-1.56 (m, 1H), 1.56 (s, 9H).

Workup

temperatureAfter cooling to ambient temperature
washthe mixture was washed with water (4×15 mL), brine (2×15 mL)
dry with materialdried over anhydrous sodium sulfate
filtrationfiltered
customAfter concentration of the filtrate in vacuo, the residue was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-d53dd9e0409d44b3b8d826e21c604b34
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952169B2

Reaction notes

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