Hydrochloric Acid → (4-Iodo-2-phenylbenzoyl)methionine methyl ester

HRID 2121186Notes

Reaction equation

HRID 2121186 reaction equation
CO[C:3](=[O:17])[C:4]1[CH:9]=[CH:8][C:7]([I:10])=[CH:6][C:5]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.Cl.Cl.[CH3:20][O:21][C:22](=[O:29])[C@H:23]([CH2:25][CH2:26][S:27][CH3:28])[NH2:24].C(N(CC)CC)C>[OH-].[Li+].CCOCC.ClCCl.CO>[CH3:20][O:21][C:22](=[O:29])[C@H:23]([CH2:25][CH2:26][S:27][CH3:28])[NH:24][C:3](=[O:17])[C:4]1[CH:9]=[CH:8][C:7]([I:10])=[CH:6][C:5]=1[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 11435579L-Methionine, methyl ester, hydrochlorideHCID 536899794-Iodo-2-phenylbenzoic acid methyl ester

Product 1

HCID 53801632(4-Iodo-2-phenylbenzoyl)methionine methyl esterYield 90%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 3939Lithium HydroxideSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of the 4-iodo-2-phenylbenzoic acid methyl ester prepared in Example 21° C. (2.77 g, 8.20 mmol) in aqueous saturated lithium hydroxide (3 mL) and methanol (10 mL) was heated at 60° C. for 12 hours. The mixture was then acidified with concentrated HCl to pH about 2, and extracted twice with ethyl acetate (50 mL each). The combine extracts was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was suspended in dichloromethane (10 mL), and oxalyl chloride (2.0 M in dichloromethane, 6.2 mL)was added, followed by a small drop of DMF. The mixture was stirred at room temperature for 1 hour, and then was concentrated in vacuo, followed by further drying under high vacuum for 10 minutes. To the residue was added dichloromethane (20 mL), L-methionine methyl ester hydrochloride (1.64 g, 8.05 mmol) and triethylamine (3.4 mL, 24.6 mmol). The reaction mixture was stirred at room temperature for 12 hours. The mixture was diluted with ether (50 mL), filtered through silica gel (30 g), and concentrated in vacuo. The crude product was purified by column chromatography (40:40:20 hexane-chloroform-ether) to give (4-iodo-2-phenylbenzoyl)methionine methyl ester (3.46 g, 90%). 1H NMR (300 MHz, CDCl3) δ 7.76 (m, 2H), 7.42 (m, 6H), 5.88 (br d, 1H), 4.65 (m, 1H), 3.68 (s, 3H), 2.05 (m, 2H), 2.00 (s, 3H), 1.90 (m, 1H), 1.73 (m, 1H).

Workup

  1. extractionextracted twice with ethyl acetate (50 mL each)
  2. washThe combine extracts was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. additionoxalyl chloride (2.0 M in dichloromethane, 6.2 mL)was added
  7. concentrationwas concentrated in vacuo
  8. customby further drying under high vacuum for 10 minutes
  9. stirringThe reaction mixture was stirred at room temperature for 12 hours
  10. filtrationfiltered through silica gel (30 g)
  11. concentrationconcentrated in vacuo
  12. customThe crude product was purified by column chromatography (40:40:20 hexane-chloroform-ether)

Sources & evidence

ORD record
ord-33afaa8e5d8e47bf83fecdcdaaf68209
Source dataset
uspto-grants-2004_02
Patent number
US06693123B2

Reaction notes

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