Water → HCID 86706691, compound

HRID 1468079Notes

Reaction equation

HRID 1468079 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7]3([CH2:16][CH2:15][CH:14]([OH:17])[CH2:13][CH2:12]3)[C:8]2=[O:11])=[CH:4][C:3]=1[CH3:18].CI.[CH3:21]C(C)([O-])C.[K+].O>[Cl-].[Na+].O>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7]3([CH2:16][CH2:15][CH:14]([O:17][CH3:21])[CH2:13][CH2:12]3)[C:8]2=[O:11])=[CH:4][C:3]=1[CH3:18]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 23665647Potassium tert-butoxide3×HCID 86706690HCID 86706690, compound2×

Product 1

HCID 86706691HCID 86706691, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

6′-Bromo-4-hydroxy-5′-methylspiro[cyclohexane-1,2′-inden]-1′(3′H)-one (Intermediate 3, 1.72 g, 5.57 mmol) was dissolved in 2-Me THF (13 mL) under an inert atmosphere and the solution was cooled to 0° C. Methyl iodide (0.453 mL, 7.24 mmol) was added followed by portionwise addition of potassium tert-butoxide (0.875 g, 7.80 mmol). The resulting mixture was stirred at r.t. for 1 h. Potassium tert-butoxide (0.250 g, 2.23 mmol) was added and stirring continued. After another 30 min, potassium tert-butoxide (0.094 g, 0.84 mmol) was added and stirring continued. After a total of 4 h, full conversion was obtained and water (6 mL) and brine (3 mL) were added. The phases were separated and the organic layer was treated with charcoal and diatomaceous earth and then filtered through a plug of diatomaceous earth. The plug was rinsed with EtOAc and the organics were concentrated to yield 1.3 g (77% yield) of the title compound as a mixture of isomers with the methoxy group in either equatorial position (major) or axial position (minor). This mixture was used in the next step without further purification: MS (ES+) m/z 323, 325 [M+H]+.

Workup

  1. stirringstirring
  2. waitAfter another 30 min
  3. stirringstirring
  4. customAfter a total of 4 h, full conversion was obtained
  5. customThe phases were separated
  6. additionthe organic layer was treated with charcoal and diatomaceous earth
  7. filtrationfiltered through a plug of diatomaceous earth
  8. washThe plug was rinsed with EtOAc
  9. concentrationthe organics were concentrated

Sources & evidence

ORD record
ord-86a3b0a13e3e445f8b00f9c87e65b942
Source dataset
uspto-grants-2015_04
Patent number
US09000183B2

Reaction notes

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