Methanamine, N-methoxy-, hydrochloride (1:1) → 5-(2-chloro-phenyl)-3-(tetrahydro-pyran-2-yloxymethyl)-isoxazole-4-carboxylic acid methoxy-N-methyl-amide

HRID 349261ノート

反応式

HRID 349261 の反応式
C([Mg]Cl)(C)C.C(O[C:9]([C:11]1[C:12]([CH2:23][O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)=[N:13][O:14][C:15]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[Cl:22])=[O:10])C.Cl.[CH3:32][NH:33][O:34][CH3:35]>C1COCC1>[CH3:35][O:34][N:33]([CH3:32])[C:9]([C:11]1[C:12]([CH2:23][O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)=[N:13][O:14][C:15]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[Cl:22])=[O:10]

参加物

5

反応物 3

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 691236215-(2-Chloro-phenyl)-3-(tetrahydro-pyran-2-yloxymethyl)-isoxazole-4-carboxylic acid ethyl esterHCID 178418918HCID 178418918、化合物

生成物 1

HCID 866012155-(2-chloro-phenyl)-3-(tetrahydro-pyran-2-yloxymethyl)-isoxazole-4-carboxylic acid methoxy-N-methyl-amide収率 52%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

Add 2M iso-propylmagnesium chloride (717 mL, 1.4 mol) to a −10° C. solution of 5-(2-chloro-phenyl)-3-(tetrahydro-pyran-2-yloxymethyl)-isoxazole-4-carboxylic acid ethyl ester (175 g, 478 mmol) and N,O-dimethylhydroxylamine hydrochloride (56 g, 574 mmol) in THF (2 L). Stir the reaction for 45 min. and then slowly quench with a 1:1 mixture of sat. NH4Cl and water (750 mL). Extract the mixture with EtOAc (3×500 mL). Wash the organic phase with brine (1000 mL), dry over Na2SO4, filter, and concentrate under reduced pressure. Purification by flash chromatography (silica gel, 7:3 hexanes/EtOAc) gives the title compound (27 g, 52%). MS (m/e): 381 (M+H)+; m.p.=51–56° C.; 1H NMR (300 MHz, CDCl3) δ7.32–7.60 (m, 4H), 5.00 (d, J=14 Hz, 1H), 4.78–4.81 (m, 1H), 4.73 (d, J=14 Hz, 1H), 3.85–3.98 (m, 1H), 3.52–3.61 (m, 1H), 3.40 (s, 3H), 3.10–3.29 (m, 3H), 1.50–1.82 (m, 6H); HPLC >99%; TLC Rf=0.41 (1:1 Hexanes/EtOAc).

後処理

  1. customthe reaction for 45 min.
  2. customslowly quench with a 1:1 mixture of sat. NH4Cl and water (750 mL)
  3. extractionExtract the mixture with EtOAc (3×500 mL)
  4. washWash the organic phase with brine (1000 mL)
  5. dry with materialdry over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate under reduced pressure
  8. customPurification by flash chromatography (silica gel, 7:3 hexanes/EtOAc)

出典と根拠

ORDレコード
ord-1b42bbf7faa847fba63004f56f48a505
出典データセット
uspto-grants-2007_02
特許番号
US07179804B2

反応ノート

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