Cesium carbonate → Tert-butyl 4-(bicyclo[4.1.0]heptan-1-ylmethoxy)-5-chloro-2-fluorobenzoate

HRID 1849782Notes

Reaction equation

HRID 1849782 reaction equation
[C:1]12([CH2:8][OH:9])[CH2:7][CH:6]1[CH2:5][CH2:4][CH2:3][CH2:2]2.[Cl:10][C:11]1[C:12](F)=[CH:13][C:14]([F:24])=[C:15]([CH:23]=1)[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O>[C:1]12([CH2:8][O:9][C:12]3[C:11]([Cl:10])=[CH:23][C:15]([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])=[C:14]([F:24])[CH:13]=3)[CH2:7][CH:6]1[CH2:5][CH2:4][CH2:3][CH2:2]2

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 10909577{Bicyclo[4.1.0]heptan-1-yl}methanolHCID 58042499tert-butyl 5-chloro-2,4-difluorobenzoate

Product 1

HCID 86703665Tert-butyl 4-(bicyclo[4.1.0]heptan-1-ylmethoxy)-5-chloro-2-fluorobenzoateYield 54%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of bicyclo[4.1.0]heptan-1-ylmethanol (0.86 g, 6.80 mmol), tert-butyl 5-chloro-2,4-difluorobenzoate (1.69 g, 6.80 mmol) and cesium carbonate (4.40 g, 13.7 mmol) in anhydrous dimethylsulfoxide (15 mL) was heated at 100° C. under nitrogen for 16 hours. The reaction mixture was filtered through a pad of diatomaceous earth and rinsed with ethyl acetate (100 mL). The organic layer was washed with 1.0 M hydrochloric acid (20 mL), dried over anhydrous sodium sulfate and concentrated in vacuo to dryness. The residue was purified by column chromatography with a mixture of hexanes in ethyl acetate (9:1) to afford the title compound as a white solid (1.30 g, 54%): 1H NMR (300 MHz, CDCl3) 7.85 (d, J=18.4 Hz, 1H), 6.54 (d, J=12.20 Hz, 1H), 3.81 (d, J=9.1 Hz, 1H), 3.68 (d, J=9.1 Hz, 1H), 1.98-1.79 (m, 4H), 1.39-1.29 (m, 3H), 1.56 (s, 9H), 1.02-0.94 (min, 1H), 0.89-0.83 (m, 1H), 0.67-0.62 (m, 1H), 0.40-0.37 (m, 1H); MS (ES+) m/z 377.2, 379.2 (M+23).

Workup

  1. filtrationThe reaction mixture was filtered through a pad of diatomaceous earth
  2. washrinsed with ethyl acetate (100 mL)
  3. washThe organic layer was washed with 1.0 M hydrochloric acid (20 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo to dryness
  6. customThe residue was purified by column chromatography with a mixture of hexanes in ethyl acetate (9:1)

Sources & evidence

ORD record
ord-7dd49a381e4f4c11b2290e4ab2834900
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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