Hydrochloric Acid → HCID 19972976, compound

HRID 1451795Notes

Reaction equation

HRID 1451795 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([NH2:18])([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[CH3:10])=[CH:4][CH:3]=1.C([NH:29][CH2:30][C:31](O)=[O:32])(OCC1C=CC=CC=1)=O.C1(N=C=NC2CCCCC2)CCCCC1.Cl>C(Cl)(Cl)Cl.CO.[Pd]>[NH2:29][CH2:30][C:31]([NH:18][C:9]([C:11]1[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=1)([CH3:10])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)=[O:32]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10868DicyclohexylcarbodiimideHCID 14349BenzyloxycarbonylglycineHCID 16061698HCID 16061698, compound

Product 1

HCID 19972976HCID 19972976, compoundYield 29.8%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6212ChloroformSolvent2×

Procedure

To a stirred solution of 1,2-bis(4-fluorophenyl)-2-propylamine (12.0 g, 0.049 mol) in chloroform (200 ml) under nitrogen was added N-CBZ-glycine (10.16 g, 0.049 mol) and then a solution of dicyclohexylcarbodiimide (11.35 g, 0.055 mol) in chloroform (100 ml) and the mixture stirred for 30 minutes, then filtered and the solvent evaporated. The residue was treated with ethyl acetate (200 ml), filtered, an additional 200 ml of ethyl acetate added, and then washed with cold 1% HCl (200 ml), brine (200 ml), dried, and the solvent evaporated to give a pale yellow oil. This was dissolved in methanol (400 ml) and 10% HCl (35 ml) and hydrogenated at 40 psi in a Parr apparatus over 2.5 g of 5% Pd/C catalyst for 2.5 hours. The catalyst was removed by filtration, solvent evaporated and the residue dissolved in water (300 ml) and chloroform (500 ml), basified to pH 11 with 50% NaOH, shaken and separated. The aqueous phase was extracted with chloroform (2×200 ml) and the combined organic phases washed with water (2×150 ml), brine (150 ml), dried and evaporated to a pale yellow oil which solidified on standing. The solid was recrystallised three times from cyclohexane (150 ml) and ethanol (10 ml) and vacuum dried to give 4.44 g of 2-amino-N-[1,2bis(4-fluorophenyl)-1-methylethyl]acetamide, mp 130°-131° C.

Workup

  1. filtrationfiltered
  2. customthe solvent evaporated
  3. additionThe residue was treated with ethyl acetate (200 ml)
  4. filtrationfiltered
  5. additionan additional 200 ml of ethyl acetate added
  6. washwashed with cold 1% HCl (200 ml), brine (200 ml)
  7. customdried
  8. customthe solvent evaporated
  9. customto give a pale yellow oil
  10. customThe catalyst was removed by filtration, solvent
  11. customevaporated
  12. dissolutionthe residue dissolved in water (300 ml)
  13. customseparated
  14. extractionThe aqueous phase was extracted with chloroform (2×200 ml)
  15. washthe combined organic phases washed with water (2×150 ml), brine (150 ml)
  16. customdried
  17. customevaporated to a pale yellow oil which
  18. customThe solid was recrystallised three times from cyclohexane (150 ml) and ethanol (10 ml) and vacuum
  19. customdried

Sources & evidence

ORD record
ord-effa0cdd9870468f98d225bd9fb763a0
Source dataset
uspto-grants-1997_02
Patent number
US05605916

Reaction notes

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