2,6-Dichlorobenzoyl chloride → N-[(2,6-dichlorophenyl)carbonyl]-4-[1,4-dimethyl-6-(trifluoromethyl)-2-oxo-3-pyridinyl]-L-phenylalanine methyl ester

HRID 895932Notes

Reaction equation

HRID 895932 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:27])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:15](=[O:26])[N:16]([CH3:25])[C:17]([C:21]([F:24])([F:23])[F:22])=[CH:18][C:19]=2[CH3:20])=[CH:10][CH:9]=1)[NH2:6].[Cl:28][C:29]1[CH:37]=[CH:36][CH:35]=[C:34]([Cl:38])[C:30]=1[C:31](Cl)=[O:32].CCN(C(C)C)C(C)C>C1COCC1.C(OCC)(=O)C>[CH3:2][O:3][C:4](=[O:27])[C@H:5]([CH2:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[C:15](=[O:26])[N:16]([CH3:25])[C:17]([C:21]([F:22])([F:23])[F:24])=[CH:18][C:19]=2[CH3:20])=[CH:12][CH:13]=1)[NH:6][C:31]([C:30]1[C:29]([Cl:28])=[CH:37][CH:36]=[CH:35][C:34]=1[Cl:38])=[O:32]

Participants

6

Reactant 3

HCID 783922,6-Dichlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 69716707HCID 69716707, compound

Product 1

HCID 69715186N-[(2,6-dichlorophenyl)carbonyl]-4-[1,4-dimethyl-6-(trifluoromethyl)-2-oxo-3-pyridinyl]-L-phenylalanine methyl esterYield 94.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a suspension of 4-[1,4-dimethyl-6-(trifluoromethyl)-2-oxo-3-pyridinyl]-L-phenylalanine methyl ester hydrochloride salt (216 mg, 0.53 mmol) and 2,6-dichlorobenzoyl chloride (120 mg, 0.57 mmol) in THF (6 mL) was added DIEA (210 μL, 1.19 mmol) at room temperature. After 5 min, a clear solution was obtained which was stirred for 18 h. Then, the mixture was diluted with ethyl acetate (50 mL). The ethyl acetate solution was washed successively with 0.5 N HCl (50 mL), saturated NaHCO3 solution (50 mL) and brine solution (50 mL) and was dried over anhydrous magnesium sulfate. Filtration of the drying agent and concentration gave crude product, which was dissolved in ethyl acetate (˜3 mL) and hexanes (˜3-4 mL) was added and stored in the refrigerator. The solid was collected and washed with hexanes. After drying under high vacuum, 270 mg (93.5% yield) of N-[(2,6-dichlorophenyl)carbonyl]-4-[1,4-dimethyl-6-(trifluoromethyl)-2-oxo-3-pyridinyl]-L-phenylalanine methyl ester was obtained a white solid: mp 170-173° C. ES-HRMS m/e calcd for C25H21Cl2F3N2O4 (M+Na) 563.0724. found 563.0730. Preparation of N-[(2,6-dichlorophenyl)carbonyl]-4-(1,4-dimethyl-6-(trifluoromethyl)-2-oxo-3-pyridinyl)-L-phenylalanine

Workup

  1. customa clear solution was obtained which
  2. washThe ethyl acetate solution was washed successively with 0.5 N HCl (50 mL), saturated NaHCO3 solution (50 mL) and brine solution (50 mL)
  3. dry with materialwas dried over anhydrous magnesium sulfate
  4. filtrationFiltration of the drying agent and concentration
  5. customgave crude product, which
  6. customThe solid was collected
  7. washwashed with hexanes
  8. customAfter drying under high vacuum

Sources & evidence

ORD record
ord-e1ff5649b718416bbdeefa26016c2a39
Source dataset
uspto-grants-2005_07
Patent number
US06916933B2

Reaction notes

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