Methyl iodide → HCID 66756619, compound

HRID 1642696Notes

Reaction equation

HRID 1642696 reaction equation
[CH:1](NC(C)C)(C)C.C([Li])CCC.[C:13]([Si:17]([CH3:29])([CH3:28])[O:18][CH:19]1[CH2:24][CH2:23][CH:22]([C:25]([OH:27])=[O:26])[CH2:21][CH2:20]1)([CH3:16])([CH3:15])[CH3:14].CI>O1CCCC1>[C:13]([Si:17]([CH3:29])([CH3:28])[O:18][CH:19]1[CH2:24][CH2:23][C:22]([CH3:1])([C:25]([OH:27])=[O:26])[CH2:21][CH2:20]1)([CH3:16])([CH3:15])[CH3:14]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 579607104-[(tert-Butyldimethylsilyl)oxy]cyclohexanecarboxylic AcidHCID 178418339Butyllithium

Product 1

HCID 66756619HCID 66756619, compoundYield 70.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a cold (−78° C.) of diisopropylamine (3.44 mL, 24.5 mmol) in tetrahydrofuran (49 mL) was added n-butyl lithium (2.5 M in hexanes, 9.81 mL, 24.5 mmol) dropwise over 10 minutes. The ice bath was removed, and the reaction mixture was allowed to warm to 0° C. and then cooled back to ±78° C. A solution of Example 45B (3.3 g, 12.3 mmol) in tetrahydrofuran (10 mL) was then added. The ice bath was removed and the reaction mixture was heated at 50° C. for 2 hours. The reaction mixture was then cooled back to ±78° C. and methyl iodide (0.84 mL, 13.5 mmol) was added followed by stirring for 2 hours. The cooling bath was removed, and the reaction mixture was stirred at room temperature for 1 hour. The reaction solution was then poured into diethyl ether (200 mL) and 1M HCl (200 mL). The layers were separated and the aqueous layer was further extracted with diethyl ether (2×200 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated to a crude yellow oil. The crude oil was purified by flash chromatography with 15% ethyl acetate/84% hexane/1% methanol to afford the titled compound (2.37 g) as a light yellow oil. MS (CI) m/z 273 (M+1)+.

Workup

  1. customThe ice bath was removed
  2. temperaturecooled back
  3. customto ±78° C
  4. customThe ice bath was removed
  5. temperaturethe reaction mixture was heated at 50° C. for 2 hours
  6. temperatureThe reaction mixture was then cooled back
  7. customto ±78° C.
  8. customThe cooling bath was removed
  9. stirringthe reaction mixture was stirred at room temperature for 1 hour
  10. additionThe reaction solution was then poured into diethyl ether (200 mL) and 1M HCl (200 mL)
  11. customThe layers were separated
  12. extractionthe aqueous layer was further extracted with diethyl ether (2×200 mL)
  13. dry with materialThe combined organic layers were dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated to a crude yellow oil
  16. customThe crude oil was purified by flash chromatography with 15% ethyl acetate/84% hexane/1% methanol

Sources & evidence

ORD record
ord-df3f4b1ae3fc48668482d2f6265bd276
Source dataset
uspto-grants-2012_02
Patent number
US08119664B2

Reaction notes

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