Ethanol → 5-Methoxy-2,3-dihydro-1H-indene-1-carbonitrile

HRID 422212Notes

Reaction equation

HRID 422212 reaction equation
[Na].CCO.[CH3:5][O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[C:12](=O)[CH2:11][CH2:10]2.S([CH2:27][N+:28]#[C-])(C1C=CC(C)=CC=1)(=O)=O>COCCOC>[CH3:5][O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[CH:12]([C:27]#[N:28])[CH2:11][CH2:10]2

Participants

6

Reactant 4

HCID 702EthanolHCID 787875-Methoxyindan-1-oneHCID 161915Tosylmethyl isocyanideHCID 5360545Sodium

Product 1

HCID 540375575-Methoxy-2,3-dihydro-1H-indene-1-carbonitrileYield 66.9%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
-5 °C

Procedure

Dissolve sodium metal (1.51 g, 66.0 mmol) in abs. EtOH (50 ml) and DME (100 ml) and add the resulting solution drop-wise to a mixture of 5-methoxy-1-indanone (3.57 g, 22.0 mmol), tosylmethyl isocyanide (6.45 g, 33.0 mmol) and DME (150 ml) cooled to −5° C. under nitrogen. After addition is complete (ca. one hour), allow mixture to slowly obtain ambient temperature and stir overnight. After cooling to 0° C., carefully quench with water and extract with EtOAc (2×). Wash the combined extracts with water and brine, dry (MgSO4) and concentrate. Purify on silica gel (toluene) to give 5-methoxy-indan-1-carbonitrile (2.55 g) as a yellow oil. 1HNMR (CDCl3): 7.31 (d, 1H), 6.80 (m, 2H), 4.05 (t, 1H), 3.80 (s, 3H), 3.07 (m, 1H), 2.93 (m, 1H), 2.56 (m, 1H), 2.39 (m, 1H).

Workup

  1. additionAfter addition
  2. custom(ca. one hour)
  3. customto slowly obtain ambient temperature
  4. temperatureAfter cooling to 0° C.
  5. customcarefully quench with water
  6. extractionextract with EtOAc (2×)
  7. washWash the combined extracts with water and brine
  8. dry with materialdry (MgSO4)
  9. concentrationconcentrate
  10. customPurify on silica gel (toluene)

Sources & evidence

ORD record
ord-819c9b001f7748a38d0d7fab47e2de28
Source dataset
uspto-grants-2012_01
Patent number
US08101638B2

Reaction notes

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