1-Chloroethyl chloroformate → HCID 69071710, compound

HRID 1822032Notes

Reaction equation

HRID 1822032 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 33%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Combine N-[3-(1-benzyl-3-methyl-piperidin-4-yloxy)-phenyl]-2-chloro-4-fluoro-benzamide cis isomer 1 (preparation 80, 0.52 g, 1.15 mmol), 1,2-dichloroethane (20 mL) and 1-chloroethyl chloroformate (1.24 mL, 11.5 mmol), stir and heat at reflux. After 2 hr., cool to ambient temperature and concentrate. Dissolve the residue in methanol (20 mL), stir and heat 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 (0.139 g, 33%). Mass spectrum: obs. m/z 363.1292; calc. m/z 363.1275; Analysis calculated for C19H21Cl2FN2O2.0.35H2O: C, 56.39; H, 5.38; N, 6.92. Found: C, 56.43; H, 5.48; N, 6.73.

Workup

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

Sources & evidence

ORD record
ord-79c6d937b1ef45f086f3bfcf5c2a8cac
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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