1-Chloroethyl chloroformate → HCID 69355594, compound

HRID 1836359Notes

Reaction equation

HRID 1836359 reaction equation
[Cl:1]C(OC(Cl)C)=O.[F:8][C:9]1[CH:32]=[CH:31][C:12]([C:13]([NH:15][C:16]2[CH:17]=[C:18]([CH:28]=[CH:29][CH:30]=2)[C:19]([CH:21]2[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]2)=[O:20])=[O:14])=[CH:11][CH:10]=1>ClCCCl>[ClH:1].[F:8][C:9]1[CH:10]=[CH:11][C:12]([C:13]([NH:15][C:16]2[CH:17]=[C:18]([CH:28]=[CH:29][CH:30]=2)[C:19]([CH:21]2[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]2)=[O:20])=[O:14])=[CH:31][CH:32]=1

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformate2×HCID 9798021HCID 9798021, compound

Product 1

HCID 69355594HCID 69355594, compoundYield 103.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

1-Chloroethyl chloroformate (435 μl, 4.0 mmol) was added dropwise to a 0° C. solution of 4-[3-(4-fluorobenzamidyl)benzoyl]-1-methylpiperidine (686 mg, 2.0 mmol) in 1,2-dichloroethane (15 ml). The reaction mixture was warmed to room temperature then heated to reflux for 1.5 h. An additional quantity of 1-chloroethyl chloroformate (400 μl, 3.7 mmol) was added and the reaction mixture was refluxed for 50 min. The reaction mixture was concentrated in vacuo. The residue was dissolved in methanol (15 mL) and heated to reflux for 2 h. The solvent was removed under vacuum to give 780 mg of a brown oil. Purification by radial chromatography (silica gel, 2000 micron rotor, methylene chloride:methanol:ammonium hydroxide, 95:5:0.5 then methylene chloride:methanol:ammonium hydroxide, 92.5:7.5:0.75) gave 220 mg (33%) of a white foam. Crystallization as the hydrochloride salt from ethyl acetate/ethanol gave a white solid. Mp>225° C. MS(m/e): 327(M+1).

Workup

  1. temperaturethen heated
  2. temperatureto reflux for 1.5 h
  3. temperaturethe reaction mixture was refluxed for 50 min
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. dissolutionThe residue was dissolved in methanol (15 mL)
  6. temperatureheated
  7. temperatureto reflux for 2 h
  8. customThe solvent was removed under vacuum

Sources & evidence

ORD record
ord-3f299eb8a44e49518679573a97542777
Source dataset
uspto-grants-2004_08
Patent number
US06777428B1

Reaction notes

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