1-Chloroethyl chloroformate → HCID 69071710, compound

HRID 1822033Notes

Reaction equation

HRID 1822033 reaction equation
C([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:16]=[C:17]([NH:21][C:22](=[O:31])[C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=3[Cl:30])[CH:18]=[CH:19][CH:20]=2)[CH:10]([CH3:32])[CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O>ClCCCl>[ClH:30].[Cl:30][C:24]1[CH:25]=[C:26]([F:29])[CH:27]=[CH:28][C:23]=1[C:22]([NH:21][C:17]1[CH:18]=[CH:19][CH:20]=[C:15]([O:14][CH:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH:10]2[CH3:32])[CH:16]=1)=[O:31]

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 69067836HCID 69067836, compound

Product 1

HCID 69071710HCID 69071710, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Dissolve N-[3-(1-benzyl-3-methyl-piperidin-4-yloxy)-phenyl]-2-chloro-4-fluoro-benzamide cis isomer 2 (preparation 81, 0.49 g, 1.09 mmol) in 1,2-dichloroethane (20 mL) and treat with 1-chloroethyl chloroformate (1.18 mL, 10.9 mmol), heat and stir at reflux. After 2 hr., cool to ambient temperature and concentrate to an oil. Dissolve residue in methanol (20 mL), heat and stir at reflux. After 1.5 hr., cool to ambient temperature. Load reaction mixture on an SCX column (10 g), wash with methanol, elute with 2M ammonia/methanol. Concentrate eluent. Purify residue by silica gel flash chromatography eluting with 10% (2M NH3/methanol)/methylene dichloride and converted to the mono hydrogen chloride salt to obtain the title compound (0.156 g, 39%). Mass spectrum: Obs. m/z 363.1281; Calc. m/z 363.1275; Analysis calculated for C19H21Cl2FN2O2.0.9H2O: C, 54.92; H, 5.53; N, 6.74. Found: C, 54.89; H, 5.33; N, 6.63.

Workup

  1. temperatureheat
  2. temperatureat reflux
  3. concentrationconcentrate to an oil
  4. temperatureDissolve residue in methanol (20 mL), heat
  5. stirringstir
  6. temperatureat reflux
  7. waitAfter 1.5 hr
  8. temperature, cool to ambient temperature
  9. customLoad reaction mixture on an SCX column (10 g)
  10. washwash with methanol
  11. washelute with 2M ammonia/methanol
  12. washPurify residue by silica gel flash chromatography eluting with 10% (2M NH3/methanol)/methylene dichloride

Sources & evidence

ORD record
ord-429d2a2c5db548dd82c69636683e3509
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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