Thionyl Chloride → HCID 59132658, compound

HRID 1160287Notes

Reaction equation

HRID 1160287 reaction equation
S(Cl)(Cl)=O.[CH3:5][C:6]1[CH:27]=[CH:26][CH:25]=[CH:24][C:7]=1[CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]([C:21]#[C:22][CH3:23])[CH2:17][C:18]([NH2:20])=O)=[CH:12][CH:11]=1>CN(C=O)C>[CH3:5][C:6]1[CH:27]=[CH:26][CH:25]=[CH:24][C:7]=1[CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]([C:21]#[C:22][CH3:23])[CH2:17][C:18]#[N:20])=[CH:12][CH:11]=1

Participants

4

Reactant 2

HCID 24386Thionyl ChlorideHCID 59132675HCID 59132675, compound

Product 1

HCID 59132658HCID 59132658, compoundYield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

An oven-dried 50 mL round-bottomed flask was charged with DMF (8 mL) and a stir bar. The solution was cooled to 0° C. in an ice bath. Thionyl chloride (160 μL, 1.0 mmol) was added slowly via syringe. The mixture was stirred at 0° C. for an additional 45 minutes. Nitrile 23.2 (300 mg, 0.98 mmol) was then added to the mixture as solution in DMF (2 mL). The reaction was stirred at 0° C. for an hour, and was then allowed to gradually warm to room temperature overnight. The reaction mixture was partitioned between ice water and ethyl acetate. The aqueous layer was extracted 2 additional times with 25 mL ethyl acetate. Saturated NaHCO3 was then added to the aqueous layer and the aqueous layer was extracted a third time with ethyl acetate. The combined organic layers were washed with saturated NaHCO3 and concentrated under reduced pressure. The resulting residue was purified via radial chromatography (15% ethyl acetate in hexanes) to yield 203 mg (72%) of 3-[4-(2-Methyl-benzyloxy)-phenyl]-hex-4-ynenitrile (23.3). 1H NMR (400 MHz) (acetone-d6) δ 7.44 (3H, m), 7.24 (3H, m), 7.05 (2H, m), 5.13 (2H, s), 4.09 (1H, m), 2.89 (2H, m), 2.39 (3H, s), 1.88 (3H, s).

Workup

  1. stirringThe reaction was stirred at 0° C. for an hour
  2. temperatureto gradually warm to room temperature overnight
  3. customThe reaction mixture was partitioned between ice water and ethyl acetate
  4. extractionThe aqueous layer was extracted 2 additional times with 25 mL ethyl acetate
  5. additionSaturated NaHCO3 was then added to the aqueous layer
  6. extractionthe aqueous layer was extracted a third time with ethyl acetate
  7. washThe combined organic layers were washed with saturated NaHCO3
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified via radial chromatography (15% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-1fe936278b804b588f26afa773bfd322
Source dataset
uspto-grants-2010_10
Patent number
US07816367B2

Reaction notes

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