Trifluoroacetic acid → 3-(4-Acetoxymethyl-7-chloro-1H-indazol-5-yl)-2-(R)-benzyloxycarbonylamino-propionic acid methyl ester

HRID 132160ノート

反応式

HRID 132160 の反応式
FC(F)(F)C(O)=O.[CH3:8][O:9][C:10](=[O:38])[C@H:11]([NH:27][C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29])[CH2:12][C:13]1[CH:18]=[C:17]([Cl:19])[C:16]([NH2:20])=[C:15]([CH3:21])[C:14]=1[CH2:22][O:23][C:24](=[O:26])[CH3:25].[N:39](OCCC(C)C)=O.C([O-])(=O)C.[K+]>C(O)(=O)C.C(Cl)(Cl)Cl.ClCCl>[CH3:8][O:9][C:10](=[O:38])[C@H:11]([NH:27][C:28]([O:30][CH2:31][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1)=[O:29])[CH2:12][C:13]1[C:14]([CH2:22][O:23][C:24](=[O:26])[CH3:25])=[C:15]2[C:16](=[C:17]([Cl:19])[CH:18]=1)[NH:20][N:39]=[CH:21]2

参加物

8

反応物 4

HCID 6422Trifluoroacetic acidHCID 8053Isoamyl NitriteHCID 517044Potassium AcetateHCID 597319483-(2-acetoxymethyl-4-amino-5-chloro-3-methyl-phenyl)-2-(R)-benzyloxycarbonylamino-propionic acid methyl ester

生成物 1

HCID 597319723-(4-Acetoxymethyl-7-chloro-1H-indazol-5-yl)-2-(R)-benzyloxycarbonylamino-propionic acid methyl ester収率 83%

試薬・触媒・溶媒 3

HCID 176Acetic Acid溶媒HCID 6212Chloroform溶媒HCID 6344Dichloromethane溶媒

実験手順

Trifluoroacetic acid (70 μL, 0.91 mmol) was added to a solution of 3-(2-acetoxymethyl-4-amino-5-chloro-3-methyl-phenyl)-2-(R)-benzyloxycarbonylamino-propionic acid methyl ester (345 mg, 0.77 mmol) in 5% acetic acid in chloroform (5.2 mL). Isoamyl nitrite (120 μL, 0.89 mmol) was added to the mixture drop-wise. Reaction mixture was stirred at room temperature for 40 minutes. Potassium acetate (300 mg, 3.1 mmol) was added to the mixture. Reaction mixture was stirred at room temperature for 45 minutes. Mixture was diluted with dichloromethane (10 mL) then washed successively with water (2×10 mL), and saturated aqueous sodium bicarbonate (2×10 mL). Organic was dried (magnesium sulfate), filtered and concentrated in vacuo. Crude product was obtained as an orange solid in 83% yield. Material was carried forward without further purification. 1H NMR (300 MHz, CDCl3): δ=8.20 (s, 1H); 7.29 (m, 5H); 7.21 (s, 1H); 5.53 (d, J=7.7, 1H); 5.40 (s, 2H); 5.04 (s, 2H); 4.67 (m, 1H); 3.74 (s, 3H); 3.34 (m, 1H); 3.21 (m, 1H); 2.02 (s, 3H). MS m/e (M+H)+=460.1.

後処理

  1. customReaction mixture
  2. customReaction mixture
  3. stirringwas stirred at room temperature for 45 minutes
  4. washthen washed successively with water (2×10 mL), and saturated aqueous sodium bicarbonate (2×10 mL)
  5. dry with materialOrganic was dried (magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customCrude product was obtained as an orange solid in 83% yield
  9. customMaterial was carried forward without further purification

出典と根拠

ORDレコード
ord-78c99016e7394d339834fbe75ff72dbc
出典データセット
uspto-grants-2008_06
特許番号
US07384930B2

反応ノート

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