Hydrochloric Acid → N-[2-[(1-Pyrrolidinylcarbonyl)amino]-5-(trifluoromethyl)benzoyl]glycine

HRID 49560Notes

Reaction equation

HRID 49560 reaction equation
[N:1]1([C:6]([NH:8][C:9]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:10]=2C(O)=O)=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.N1CCCC1.CN1CC[O:31][CH2:30]C1.Cl.C([O:42][C:43](=[O:46])[CH2:44][NH2:45])C1C=CC=CC=1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.Cl>CN(C=O)C.CCOC(C)=O>[N:1]1([C:6]([NH:8][C:9]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:10]=2[C:30]([NH:45][CH2:44][C:43]([OH:42])=[O:46])=[O:31])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 31268PyrrolidineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 11701227Benzyl 2-aminoacetate hydrochlorideHCID 221431222-(Pyrrolidinylcarbonyl)amino-5-trifluoromethylbenzoic acid

Product 1

HCID 21991137N-[2-[(1-Pyrrolidinylcarbonyl)amino]-5-(trifluoromethyl)benzoyl]glycine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

2-(Pyrrolidinylcarbonyl)amino-5-trifluoromethylbenzoic acid (made analogously to Example 116 with pyrrolidine in place of iso-butylamine (2.9 g) was dissolved in DMF (40 mL). After cooling to 0° C., 4-methylmorpholine (3.2 mL) and glycine benzyl ester hydrogen chloride (5.6 g) were added. After 5 min, BOP Reagent (5.6 g) was added and the mixture was stirred at rt for 18 h. EtOAc was added along with 1 N HCl solution. The EtOAc layer was washed with 1 N HCl, NaHCO3 solution, and brine. The EtOAc was dried (MgSO4), filtered, and concentrated to a solid (2.6 g). This solid was dissolved in MeOH (14 mL) prior to the addition of 10% Pd/C. A hydrogen balloon was added and the solution was stirred for 1 h. The palladium was filtered and the solution was concentrated to give the title glycine derivative (2.0 g) as a white solid. MS found: (M+H)+=360.2.

Workup

  1. washThe EtOAc layer was washed with 1 N HCl, NaHCO3 solution, and brine
  2. dry with materialThe EtOAc was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated to a solid (2.6 g)
  5. dissolutionThis solid was dissolved in MeOH (14 mL)
  6. additionto the addition of 10% Pd/C
  7. additionA hydrogen balloon was added
  8. stirringthe solution was stirred for 1 h
  9. filtrationThe palladium was filtered
  10. concentrationthe solution was concentrated

Sources & evidence

ORD record
ord-945bbde546ad490c90d9d0f5dce0de13
Source dataset
uspto-grants-2004_03
Patent number
US06706712B2

Reaction notes

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