Benzylamine → (s)-2-(2-Benzylamino-5-trifluoromethyl-benzoylamino)-butyric acid tert-butyl ester

HRID 1091446Notes

Reaction equation

HRID 1091446 reaction equation
[C:1]([O:5][C:6](=[O:24])[C@@H:7]([NH:10][C:11](=[O:23])[C:12]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:13]=1Cl)[CH2:8][CH3:9])([CH3:4])([CH3:3])[CH3:2].ClC1C=CC(C(F)(F)F)=CC=1C(O)=O.N[C@@H](CC)C(OC(C)(C)C)=O.[CH2:50]([NH2:57])[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.C(=O)([O-])[O-].[K+].[K+]>CN1CCCC1.[Cl-].[NH4+].[Cu].[Cu]Br>[C:1]([O:5][C:6](=[O:24])[C@@H:7]([NH:10][C:11](=[O:23])[C:12]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:13]=1[NH:57][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)[CH2:8][CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

10

Reactant 5

HCID 7504BenzylamineHCID 11430Potassium CarbonateHCID 6881822-Chloro-5-(trifluoromethyl)benzoic acidHCID 7019938(2S)-2-amino butanic acid t-butyl esterHCID 66593952(s)-2-(2-Chloro-5-trifluoromethyl-benzoylamino)-butyric acid tert-butyl ester

Product 1

HCID 57725377(s)-2-(2-Benzylamino-5-trifluoromethyl-benzoylamino)-butyric acid tert-butyl ester

Reagents, catalysts & solvents 4

HCID 23978CopperCatalystHCID 24593copper(I) bromideCatalystHCID 84541-MethylpyrrolidineSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
160 °C

Procedure

To a solution of (S)-2-(2-chloro-5-trifluoromethyl-benzoylamino)-butyric acid tert-butyl ester (prepared from 2-chloro5-trifluoromethylbenzoic acid and (S)-2-aminobutyric acid, tert butyl ester in a procedure similar to that described in method F) (3 g) and benzylamine (1.1 ml) in N-methylpyrrolidine (40 ml) was added potassium carbonate (1.6 g), copper (30 mg) and copper (I) bromide (15 mg). The mixture was heated at 160° C. for 3 hours then cooled to room temp. and diluted with saturated ammonium chloride solution. The mixture was extracted with ethyl acetate and the organic solution dried (magnesium sulfate), filtered and concentrated. The residue was purified on silica gel, eluting with 15% ethyl acetate/hexane. The sub-titled product was obtained as a white solid (950 mg, 27%). 1H NMR (400 MHz, CDCl3) δ 1.04 (3H, t), 1.50 (9H, s), 2.86 (1H, m), 2.02 (1H, m), 4.50 (2H, d), 4.65 (1H, m), 6.69 (2H, m), 7.21-7.70 (7H, m), 8.42 (1H, m) ppm; MS ES (−) 435.32 (M−H).

Workup

  1. temperaturethen cooled to room temp.
  2. extractionThe mixture was extracted with ethyl acetate
  3. dry with materialthe organic solution dried (magnesium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified on silica gel
  7. washeluting with 15% ethyl acetate/hexane

Sources & evidence

ORD record
ord-cd13b8842f9346ad826b7085cca4aab8
Source dataset
uspto-grants-2012_03
Patent number
US08129381B2

Reaction notes

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