Hydrochloric Acid → HCID 178516771, compound

HRID 538063Notes

Reaction equation

HRID 538063 reaction equation
Cl[CH2:2][C:3](Cl)=[O:4].C(O)(=O)C.C[O:11][C:12]([C@H:14]1[CH2:19][CH2:18][C@H:17]([CH2:20][NH:21][C:22](=[O:30])[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[NH2:29])[CH2:16][CH2:15]1)=[O:13].Cl.[H-].[Na+].[Cl-].[NH4+]>C(Cl)Cl.CN(C=O)C>[O:4]=[C:3]1[NH:29][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[C:22](=[O:30])[N:21]([CH2:20][C@H:17]2[CH2:18][CH2:19][C@H:14]([C:12]([OH:13])=[O:11])[CH2:15][CH2:16]2)[CH2:2]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6577Chloroacetyl chlorideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 178476671HCID 178476671, compound

Product 1

HCID 178516771HCID 178516771, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
80 °C

Procedure

A solution of chloroacetyl chloride (470 μL) in dry DCM (6 mL) was added dropwise to a stirred solution of trans-4-[(2-Amino-benzoylamino)-methyl]-cyclohexanecarboxylic acid methyl ester acetate (3 mmol, 0.850 g) and TEA (9 mmol, 1.2 mL) in dry DCM (44 mL) under argon at 0° C. The mixture was allowed to reach room temperature within 30 minutes. After reaction completion, the reaction mixture was poured into 2N HCl solution (10 mL) and extracted with DCM (3×40 mL). The organic layer was washed with a saturated solution of NaHCO3 (1×30 mL) and brine (2×30 mL). Finally, the solvent was removed under reduced pressure. NaH (60% on mineral oil 13.5 mmol, 0.54 g) was added to a solution of the crude product in dry DMF (11 mL) and the mixture was heated at 80° C. for 4 h, then the reaction mixture was allowed to reach room temperature. A saturated ammonium chloride solution (10 mL) was added to the mixture and the final mixture was washed with DCM (2×20 mL) and then the mixture was acidified with (2 N) HCl and extracted with DCM (3×10 mL). The organic layer was washed with brine (2×10 mL) dried over Na2SO4 anhydrous, concentrated under reduced pressure and filtrate on silica pad. The silica pad was washed 3 times with a DCM-MeOH 95-5 all the washings were collected together and the solvent was removed under reduced pressure to afford the titled compound (0.49 g, yield 57%).

Workup

  1. customAfter reaction completion
  2. extractionextracted with DCM (3×40 mL)
  3. washThe organic layer was washed with a saturated solution of NaHCO3 (1×30 mL) and brine (2×30 mL)
  4. customFinally, the solvent was removed under reduced pressure
  5. customto reach room temperature
  6. washthe final mixture was washed with DCM (2×20 mL)
  7. extractionextracted with DCM (3×10 mL)
  8. washThe organic layer was washed with brine (2×10 mL)
  9. dry with materialdried over Na2SO4 anhydrous
  10. concentrationconcentrated under reduced pressure and filtrate on silica pad
  11. washThe silica pad was washed 3 times with a DCM-MeOH 95-5 all the washings
  12. customwere collected together
  13. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-cc2a092d1920499e8d3bbccee20c6916
Source dataset
uspto-grants-2014_10
Patent number
US08865704B2

Reaction notes

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