Methyl iodide → HCID 118062643, compound

HRID 920801Notes

Reaction equation

HRID 920801 reaction equation
[Li+].[CH3:2]C([N-]C(C)C)C.[CH2:9]1[C:11]2([CH2:14][CH:13]([C:15]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:16])[CH2:12]2)[CH2:10]1.CI>C1COCC1>[CH3:2][C:13]1([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:12][C:11]2([CH2:10][CH2:9]2)[CH2:14]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2724682Lithium diisopropylamideHCID 118061850HCID 118061850, compound

Product 1

HCID 118062643HCID 118062643, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of LDA (3.47 mL, 6.94 mmol 2M in THF) in THF (5 mL) cooled to −78° C., was added dropwise a solution of benzyl spiro[2.3]hexane-5-carboxylate (0.5 g, 2.312 mmol) in THF (2 mL). The resulting solution was stirred for 30 min. prior to the dropwise addition of MeI (0.723 mL, 11.56 mmol) at −78° C. The resulting reaction mixture was allowed to warm to RT and stir for 12 h. The reaction mixture was quenched with a saturated aq. solution of NH4Cl (20 mL) and extracted with EtOAc (3×10 mL) The combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by silica gel chromatography (24 g REDISEP® column, eluting with 5% EtOAc in hexanes). Fractions containing the product were combined and evaporated to afford the Intermediate 317A as a colorless liquid (200 mg, 38% yield). MS(ES): m/z=231.2 [M+H]+; 1H NMR (400 MHz, chloroform-d) δ ppm 7.50-7.28 (m, 5H), 5.36-4.94 (s, 2H), 2.87-2.47 (m, 2H), 2.01-1.77 (m, 2H), 1.62-1.39 (s, 3H), 0.60-0.22 (m, 4H).

Workup

  1. customThe resulting reaction mixture
  2. stirringstir for 12 h
  3. customThe reaction mixture was quenched with a saturated aq. solution of NH4Cl (20 mL)
  4. extractionextracted with EtOAc (3×10 mL) The combined organic layer
  5. washwas washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by silica gel chromatography (24 g REDISEP® column, eluting with 5% EtOAc in hexanes)
  10. additionFractions containing the product
  11. customevaporated

Sources & evidence

ORD record
ord-de19ef939b9647bf9152a6c2f9aba9b0
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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