Triphosgene → (5R)-5-ethyl-5-methyl-3-[6-[(2,4,4-trimethyl-3,1-benzoxazin-5-yl)oxy]-3-pyridyl]imidazolidine-2,4-dione

HRID 527716ノート

反応式

HRID 527716 の反応式
[NH2:1][C@:2]([CH3:28])([CH2:26][CH3:27])[C:3]([NH:5][C:6]1[CH:7]=[N:8][C:9]([O:12][C:13]2[C:18]3[C:19]([CH3:25])([CH3:24])[O:20][C:21]([CH3:23])=[N:22][C:17]=3[CH:16]=[CH:15][CH:14]=2)=[CH:10][CH:11]=1)=[O:4].Cl[C:30](Cl)([O:32]C(=O)OC(Cl)(Cl)Cl)Cl>C(OCC)(=O)C.O>[CH2:26]([C@@:2]1([CH3:28])[NH:1][C:30](=[O:32])[N:5]([C:6]2[CH:7]=[N:8][C:9]([O:12][C:13]3[C:18]4[C:19]([CH3:25])([CH3:24])[O:20][C:21]([CH3:23])=[N:22][C:17]=4[CH:16]=[CH:15][CH:14]=3)=[CH:10][CH:11]=2)[C:3]1=[O:4])[CH3:27]

参加物

5

反応物 2

HCID 94429TriphosgeneHCID 67959970(2R)-2-amino-2-methyl-N-[6-[(2,4,4-trimethyl-3,1-benzoxazin-5-yl)oxy]-3-pyridyl]butanamide2 回

生成物 1

HCID 57411185(5R)-5-ethyl-5-methyl-3-[6-[(2,4,4-trimethyl-3,1-benzoxazin-5-yl)oxy]-3-pyridyl]imidazolidine-2,4-dione収率 187.7%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒3 回

反応条件

温度
0 °C

実験手順

To a solution of (2R)-2-amino-2-methyl-N-[6-[(2,4,4-trimethyl-3,1-benzoxazin-5-yl)oxy]-3-pyridyl]butanamide (Intermediate 205, 143 mg, 0.37 mmol) and TEA (0.21 mL) in ethyl acetate (2.5 mL) at 0° C., triphosgene (44 mg, 0.15 mmol) dissolved in ethyl acetate (2.5 mL) was added drop wise in 10 min. The reaction mixture was stirred at 0° C. for 40 min. The reaction mixture was diluted with water (5 mL) and ethyl acetate (10 mL). Phases were separated and the aqueous was back-extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (15 mL), dried over Na2SO4, filtered and concentrated and the residue was purified by flash chromatography on silica gel using ethyl acetate as eluent affording the title compound (115 mg) as white solid.

後処理

  1. additionwas added drop wise in 10 min
  2. customPhases were separated
  3. extractionthe aqueous was back-extracted with ethyl acetate (2×10 mL)
  4. washThe combined organic layers were washed with brine (15 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe residue was purified by flash chromatography on silica gel

出典と根拠

ORDレコード
ord-f2c74c2b39124f288bb3fae07153c34c
出典データセット
uspto-grants-2016_05
特許番号
US09346790B2

反応ノート

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