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

HRID 2121186ノート

反応式

HRID 2121186 の反応式
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

参加物

9

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 3283Diethyl Ether溶媒HCID 3939Lithium Hydroxide溶媒HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-33afaa8e5d8e47bf83fecdcdaaf68209
出典データセット
uspto-grants-2004_02
特許番号
US06693123B2

反応ノート

読み込み中…