Iodoethane → HCID 118062312, compound

HRID 920777Notes

Reaction equation

HRID 920777 reaction equation
[F:1][C:2]1([F:16])[CH2:5][CH:4]([C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])[CH2:3]1.[CH2:17](I)[CH3:18].C[Si]([N-][Si](C)(C)C)(C)C.[K+]>C1COCC1>[CH2:17]([C:4]1([C:6]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:7])[CH2:3][C:2]([F:16])([F:1])[CH2:5]1)[CH3:18]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 56592986Benzyl 3,3-difluorocyclobutane-1-carboxylate

Product 1

HCID 118062312HCID 118062312, compoundYield 35.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of benzyl 3,3-difluorocyclobutanecarboxylate (500 mg, 2.210 mmol) and EtI (0.714 mL, 8.84 mmol) in THF (15 mL) at −78° C. under a N2 atmosphere was added a solution of KHMDS (8.84 mL, 4.42 mmol, 0.5 M in toluene). The resulting solution was stirred at −78° C. for 6 h. The reaction was then allowed to warm to RT and stirred overnight. The reaction mass was then quenched with a saturated aq. solution of NH4Cl and the aqueous layer was extracted with diethyl ether (3×25 mL) The combined organic fractions were washed with water, dried over Na2SO4, filtered and concentrated under vacuum. The crude product was purified by silica gel chromatography (4 g REDISEP® column, eluting with 15% EtOAc in hexanes). Fractions containing the product were combined and evaporated to afford Intermediate 301A as a pale yellow liquid (200 mg, 35.6%). 1H NMR (300 MHz, chloroform-d) δ ppm 7.32-7.44 (m, 5H), 5.19 (s, 2H), 2.90-3.11 (m, 2H), 2.38-2.57 (m, 2H), 1.28 (dt, J=8.97, 7.03 Hz, 2H), 0.79-0.93 (m, 3H).

Workup

  1. temperatureto warm to RT
  2. stirringstirred overnight
  3. customThe reaction mass was then quenched with a saturated aq. solution of NH4Cl
  4. extractionthe aqueous layer was extracted with diethyl ether (3×25 mL) The combined organic fractions
  5. washwere washed with water
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe crude product was purified by silica gel chromatography (4 g REDISEP® column, eluting with 15% EtOAc in hexanes)
  10. additionFractions containing the product
  11. customevaporated

Sources & evidence

ORD record
ord-ca6ae39023e3481b88c3503d385d4d59
Source dataset
uspto-grants-2016_03
Patent number
US09273058B2

Reaction notes

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