Triethylamine → 2-[Cyclopropyl-(3-morpholin-4-yl-5-trifluoromethyl-benzoyl)-amino]-3-oxo-butyric acid ethyl ester

HRID 545358Notes

Reaction equation

HRID 545358 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:14])[CH:6]([NH:10][CH:11]1[CH2:13][CH2:12]1)[C:7](=[O:9])[CH3:8])[CH3:3].[N:15]1([C:21]2[CH:22]=[C:23]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=2)[C:24](O)=[O:25])[CH2:20][CH2:19][O:18][CH2:17][CH2:16]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C>CN(C=O)C>[CH2:2]([O:4][C:5](=[O:14])[CH:6]([N:10]([CH:11]1[CH2:12][CH2:13]1)[C:24](=[O:25])[C:23]1[CH:27]=[C:28]([C:30]([F:31])([F:32])[F:33])[CH:29]=[C:21]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[CH:22]=1)[C:7](=[O:9])[CH3:8])[CH3:3]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 220579413-Morpholin-4-yl-5-trifluoromethyl-benzoic acidHCID 671330592-Cyclopropylamino-3-oxo-butyric acid ethyl ester hydrochloride salt

Product 1

HCID 671332092-[Cyclopropyl-(3-morpholin-4-yl-5-trifluoromethyl-benzoyl)-amino]-3-oxo-butyric acid ethyl esterYield 93%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 0.4 g (2 mmol) of 2-cyclopropylamino-3-oxo-butyric acid ethyl ester hydrochloride salt, 0.6 g (2 mmol) of 3-morpholin-4-yl-5-trifluoromethyl-benzoic acid, 0.4 g (2 mmol) of EDCI and 0.3 g (2 mmol) of HOBT was added 2 ml of DMF and 0.6 ml (4 mmol) of triethylamine. The mixture was stirred for 3 h after which time the solvent was removed by evaporation; the residue was then re-dissolved in EtOAc, washed with 10% citric acid solution, saturated sodium hydrogen carbonate solution, dried with sodium sulfate and re-concentrated to afford 0.8 g (93%) of crude 2-[cyclopropyl-(3-morpholin-4-yl-5-trifluoromethyl-benzoyl)-amino]-3-oxo-butyric acid ethyl ester. This material was re-dissolved in 5 ml of EtOH and 1 g (8 mmol) of ammonium trifluoroacetate was added. The solvent was evaporated and the residue heated to 130° C. for 16 h. The cooled residue was partitioned between saturated sodium hydrogen carbonate solution and CH2Cl2. The organic phase was dried with sodium sulfate and concentrated. Purification by flash column chromatography [n-heptane/EtOAc 6:4] afforded 0.4 g (55%) of the title compound as colorless solid. MS: 424.2 (MH+).

Workup

  1. customwas removed by evaporation
  2. dissolutionthe residue was then re-dissolved in EtOAc
  3. washwashed with 10% citric acid solution, saturated sodium hydrogen carbonate solution
  4. dry with materialdried with sodium sulfate
  5. concentrationre-concentrated

Sources & evidence

ORD record
ord-820ba63abaf149b9bdb2639d751d93a9
Source dataset
uspto-grants-2011_05
Patent number
US07935707B2

Reaction notes

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