Chloroform → 2-(2-Naphthyl)acetyl chloride

HRID 566231Notes

Reaction equation

HRID 566231 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][C:12]([OH:14])=O.C(Cl)(Cl)[Cl:16]>>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][C:12]([Cl:16])=[O:14]

Participants

3

Reactant 2

HCID 6212Chloroform2×HCID 113932-Naphthaleneacetic acid

Product 1

HCID 5881152-(2-Naphthyl)acetyl chloride

Procedure

2-Naphthylacetyl chloride is prepared according to the method described in Example 8 using 2-naphthylacetic acid (2.47 g, 13.3 mmol) to give a yellow solid which is dissolved in chloroform (15 mL). This solution is added to a solution of (±)-trans-[2-(4-methyl-1-piperazinyl)]cyclohexanol (2.5 g, 12.6 mmol) in chloroform (10 mL), and the mixture is refluxed for 11 hours under nitrogen. The solvent is removed in vacuo, and the residue is partitioned between 1M hydrochloric acid (100 mL) and ether (60 mL). The ether layer is separated and the aqueous is washed with more ether (2×30 mL), and then basified by the addition of 50% sodium hydroxide solution. This is then extracted with ether (4×30 mL), and the combined ether extracts are washed repeatedly with water to remove any unreacted aminoalcohol. The ether containing the product is then dried over sodium sulfate, and the solvent is removed to leave the crude free ester. The free ester is dissolved in ether/dichloromethane (35 mL, 4:3) and converted to the dihydrochloride salt by treatment with an excess of HCl in the same solvent. The resulting solid is washed with ether and recrystallised from hot methanol to yield the title compound.

Workup

  1. customto give a yellow solid which
  2. temperaturethe mixture is refluxed for 11 hours under nitrogen
  3. customThe solvent is removed in vacuo
  4. customthe residue is partitioned between 1M hydrochloric acid (100 mL) and ether (60 mL)
  5. customThe ether layer is separated
  6. washthe aqueous is washed with more ether (2×30 mL)
  7. additionbasified by the addition of 50% sodium hydroxide solution
  8. extractionThis is then extracted with ether (4×30 mL)
  9. washthe combined ether extracts are washed repeatedly with water
  10. customto remove any unreacted aminoalcohol
  11. dry with materialThe ether containing the product is then dried over sodium sulfate
  12. customthe solvent is removed
  13. customto leave the crude free ester

Sources & evidence

ORD record
ord-7b54dee083ec44deb9a8a06c90ba023a
Source dataset
uspto-grants-2001_01
Patent number
US06174879B1

Reaction notes

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