Cesium carbonate → HCID 86703556, compound

HRID 1849685Notes

Reaction equation

HRID 1849685 reaction equation
[CH3:1][C:2]1([CH2:12][OH:13])[CH2:11][CH2:10][C:5]2([O:9][CH2:8][CH2:7][O:6]2)[CH2:4][CH2:3]1.[Cl:14][C:15]1[C:16](F)=[CH:17][C:18]([F:28])=[C:19]([CH:27]=1)[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O>[Cl:14][C:15]1[C:16]([O:13][CH2:12][C:2]2([CH3:1])[CH2:11][CH2:10][C:5]3([O:6][CH2:7][CH2:8][O:9]3)[CH2:4][CH2:3]2)=[CH:17][C:18]([F:28])=[C:19]([CH:27]=1)[C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 12568263(8-Methyl-1,4-dioxaspiro(4.5)decan-8-yl)methanolHCID 58042499tert-butyl 5-chloro-2,4-difluorobenzoate

Product 1

HCID 86703556HCID 86703556, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of (8-methyl-1,4-dioxaspiro[4.5]decan-8-yl)methanol (4.30 g, 23 mmol) and tert-butyl 5-chloro-2,4-difluorobenzoate (10.66 g, 30 mmol) in anhydrous dimethylsulfoxide (37 mL) was added cesium carbonate (14.99 g, 46 mmol). The reaction mixture was heated to 70° C. and stirred for 4 days. At this point, HPLC and TLC analysis indicated remaining starting material, but the reaction was not progressing any further. The reaction mixture was cooled to ambient temperature, filtered through a pad of diatomaceous earth and rinsed with ethyl acetate (100 mL). The filtrate was washed with 1N aqueous hydrochloric acid solution (100 mL). The organic layer was separated, washed with brine (40 ml), dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (0% to 20% ethyl acetate in hexanes) afforded the title compound (5.13 g, 54%) as a colorless oil: MS (ES+) m/z 359.1 (M−55).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. filtrationfiltered through a pad of diatomaceous earth
  3. washrinsed with ethyl acetate (100 mL)
  4. washThe filtrate was washed with 1N aqueous hydrochloric acid solution (100 mL)
  5. customThe organic layer was separated
  6. washwashed with brine (40 ml)
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by column chromatography (0% to 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-a2b227ddf0204fce96ce2b0e7eaf4ba5
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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