1,2-Dichloroethane → HCID 69069960, compound

HRID 1822052Notes

Reaction equation

HRID 1822052 reaction equation
Cl.[F:2][C:3]1[CH:25]=[CH:24][C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH:17]3[CH2:22][CH2:21][N:20](C)[CH2:19][CH2:18]3)[N:11]=2)=[O:8])=[CH:5][CH:4]=1.[Cl:26]CCCl.ClC(OC(Cl)C)=O.[Cl-].[NH4+]>CO>[ClH:26].[F:2][C:3]1[CH:4]=[CH:5][C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH:17]3[CH2:18][CH2:19][NH:20][CH2:21][CH2:22]3)[N:11]=2)=[O:8])=[CH:24][CH:25]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 25517Ammonium ChlorideHCID 5213051-Chloroethyl chloroformate2×HCID 69067478HCID 69067478, compound

Product 1

HCID 69069960HCID 69069960, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
80 °C

Procedure

Combine 4-fluoro-N-[6-(1-methyl-piperidin-4-yloxy)-pyridin-2-yl]-benzamide hydrochloride (example 161, 365 mg, 1.11 mmol) and 1,2-dichloroethane (10 mL) and add 1-chloroethyl chloroformate (1.20 mL, 11.1 mmol). Heat the reaction to 80° C. for 18 hr. Add additional 1-chloroethyl chloroformate (600 μL, 5.5 mmol) and continue to heat at 80° C. for 5 hr. Cool reaction to ambient temperature and add methanol. Load solution onto an SCX column and wash with methanol. Flush off product with 2 M ammonia in methanol and concentrate in vacuo. Purify by column chromatography (2%-8% 2 M NH3 in methanol/CH2Cl2). Make the hydrogen chloride salt by sonication with one equivalent of ammonium chloride dissolved in methanol to yield of the title compound (115 mg, 29%). Mass spectrum (ion spray): m/z 316.3 (M+1); Analysis calculated for C17H19N3O2FCl.0.5H2O. Theory: C, 56.59; H, 5.59; N, 11.65. Found: C, 56.83; H, 5.38; N, 11.74. mp=251-3° C.

Workup

  1. temperatureHeat
  2. customthe reaction to 80° C. for 18 hr
  3. temperatureCool
  4. customreaction to ambient temperature
  5. washLoad solution onto an SCX column and wash with methanol
  6. customFlush off product with 2 M ammonia in methanol
  7. concentrationconcentrate in vacuo
  8. customPurify by column chromatography (2%-8% 2 M NH3 in methanol/CH2Cl2)

Sources & evidence

ORD record
ord-09f63b51465d48fcb5981697199d75d1
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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