Cesium carbonate → HCID 86703470, compound

HRID 1849615Notes

Reaction equation

HRID 1849615 reaction equation
[F:1][C:2]1([F:11])[CH2:7][CH2:6][C:5]([CH2:9][OH:10])([CH3:8])[CH2:4][CH2:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:18][C:19]1[C:20](F)=[CH:21][C:22]([F:32])=[C:23]([CH:31]=1)[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25]>CS(C)=O.C(OCC)(=O)C>[Cl:18][C:19]1[C:20]([O:10][CH2:9][C:5]2([CH3:8])[CH2:4][CH2:3][C:2]([F:11])([F:1])[CH2:7][CH2:6]2)=[CH:21][C:22]([F:32])=[C:23]([CH:31]=1)[C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 58042499tert-butyl 5-chloro-2,4-difluorobenzoateHCID 66583003HCID 66583003, compound

Product 1

HCID 86703470HCID 86703470, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of (4,4-difluoro-1-methylcyclohexyl)methanol (3.05 g, 18.56 mmol)(PCT Int. Appl., WO2012025857, 2012), cesium carbonate (12.09 g, 37.12 mmol), and tert-butyl 5-chloro-2,4-difluorobenzoate (6.0 g, 24.13 mmol) in dimethylsulfoxide (70 mL) was stirred at 70° C. for 16 hours, cooled to ambient temperature and diluted with ethyl acetate (150 mL); washed with water (2×300 mL), brine (150 mL); dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Purification of the residue by column chromatography eluting with a gradient of ethyl acetate in hexanes (0-5%) afforded the title compound (3.69 g, 51%) as colorless oil: MS (ES+) m/z 393.1 (M+1).

Workup

  1. temperaturecooled to ambient temperature
  2. washwashed with water (2×300 mL), brine (150 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by column chromatography
  7. washeluting with a gradient of ethyl acetate in hexanes (0-5%)

Sources & evidence

ORD record
ord-1849260f8013423dbda626100eff59cf
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

Loading…