Ammonium Chloride → N-(2,6-dichlorobenzoyl)-4-(2-cyano-3-thienyl)-L-phenylalanine methyl ester

HRID 24673Notes

Reaction equation

HRID 24673 reaction equation
[CH3:1][O:2][C:3](=[O:31])[C@H:4]([CH2:16][C:17]1[CH:22]=[CH:21][C:20](OS(C(F)(F)F)(=O)=O)=[CH:19][CH:18]=1)[NH:5][C:6](=[O:15])[C:7]1[C:12]([Cl:13])=[CH:11][CH:10]=[CH:9][C:8]=1[Cl:14].C[Sn](C)(C)[C:34]1[CH:38]=[CH:37][S:36][C:35]=1[C:39]#[N:40].[Li+].[Cl-].[NH4+].[Cl-]>O1CCOCC1.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3](=[O:31])[C@H:4]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:34]2[CH:38]=[CH:37][S:36][C:35]=2[C:39]#[N:40])=[CH:19][CH:18]=1)[NH:5][C:6](=[O:15])[C:7]1[C:8]([Cl:14])=[CH:9][CH:10]=[CH:11][C:12]=1[Cl:13]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 433294Lithium ChlorideHCID 21986264HCID 21986264, compoundHCID 22970630HCID 22970630, compound

Product 1

HCID 53922803N-(2,6-dichlorobenzoyl)-4-(2-cyano-3-thienyl)-L-phenylalanine methyl esterYield 38%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N-(2,6-dichlorobenzoyl)-O-(trifluoromethane sulfonyl)-L-tyrosine methyl ester (361 mg), trimethyl(2-cyano-3-thienyl)tin (393 mg), Pd(PPh3)4 (42 mg) and LiCl (93 mg) in dioxane (8 mL) was stirred at 100° C. under N2 for 38 h. The mixture was diluted with AcOEt and treated with 10% NH4Cl aqueous solution (6 mL). After stirring at room temperature for 1 h, the mixture was filtered through Celite and washed with AcOEt. The combined organic layers were washed successively with water and brine, dried (MgSO4) and evaporated under reduced pressure. The residue was purified by silica gel chromatography to afford N-(2,6-dichlorobenzoyl)-4-(2-cyano-3-thienyl)-L-phenylalanine methyl ester (126 mg). ESMS m/z 481 (M++Na), 459 (MH+), 457 (M−H)−.

Workup

  1. stirringAfter stirring at room temperature for 1 h
  2. filtrationthe mixture was filtered through Celite
  3. washwashed with AcOEt
  4. washThe combined organic layers were washed successively with water and brine
  5. dry with materialdried (MgSO4)
  6. customevaporated under reduced pressure
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-5e08f58803cd4e678e8059227ae87f74
Source dataset
uspto-grants-2005_02
Patent number
US06855843B2

Reaction notes

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