Potassium tert-butoxide → Methyl 5-chloro-2-fluoro-4-((4-methylenecyclohexyl)oxy)benzoate

HRID 1849916Notes

Reaction equation

HRID 1849916 reaction equation
[CH3:1]C(C)([O-])C.[K+].[Cl:7][C:8]1[C:9]([O:19][CH:20]2[CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]2)=[CH:10][C:11]([F:18])=[C:12]([CH:17]=1)[C:13]([O:15][CH3:16])=[O:14]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1.O>[Cl:7][C:8]1[C:9]([O:19][CH:20]2[CH2:25][CH2:24][C:23](=[CH2:1])[CH2:22][CH2:21]2)=[CH:10][C:11]([F:18])=[C:12]([CH:17]=1)[C:13]([O:15][CH3:16])=[O:14]

Participants

6

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 86703687Methyl 5-chloro-2-fluoro-4-((4-oxocyclohexyl)oxy)benzoate

Product 1

HCID 86703796Methyl 5-chloro-2-fluoro-4-((4-methylenecyclohexyl)oxy)benzoateYield 83.3%

Reagents, catalysts & solvents 3

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a suspension of methyltriphenylphosphonium bromide (1.61 g, 4.51 mmol) in anhydrous tetrahydrofuran (20 mL) was added a solution of potassium tert-butoxide (0.541 g, 4.82 mmol) in anhydrous tetrahydrofuran (15 mL) dropwise over 3 minutes at 0° C. The mixture was stirred under a nitrogen atmosphere at 0° C. for 1 h. To this solution was added a solution of methyl 5-chloro-2-fluoro-4-((4-oxocyclohexyl)oxy)benzoate (1.05 g, 3.48 mmol) in anhydrous tetrahydrofuran (15 mL) dropwise over 3 minutes. The mixture was stirred at ambient temperature for 21 h, then diluted with water (200 mL). The mixture was extracted with ethyl acetate (200 mL) and the organic phase was washed with water (50 mL) and brine (150 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography with a gradient of 0-10% ethyl acetate in hexanes to afford the title compound as a colorless syrup (0.866 g, 83% yield): 1H NMR (300 MHz, CDCl3) δ 7.94 (d, J=7.7 Hz, 1H), 6.67 (d, J=12.2 Hz, 1H), 4.68 (s, 2H), 4.56-4.50 (m, 1H), 3.87 (s, 3H), 2.48-2.40 (m, 2H), 2.17-2.09 (m, 2H), 1.92-1.86 (m, 4H); MS (ES+) m/z 299.00 (M+1).

Workup

  1. stirringThe mixture was stirred at ambient temperature for 21 h
  2. extractionThe mixture was extracted with ethyl acetate (200 mL)
  3. washthe organic phase was washed with water (50 mL) and brine (150 mL)
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography with a gradient of 0-10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-6ecaa4680b5f47b990b39ed4ace75ac4
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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