1,4-Dioxane → (R)-2-(3-chloro-phenyl)-morpholine hydrochloride

HRID 530594ノート

反応式

HRID 530594 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O1CCOCC1>Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3].[ClH:20].[Cl:20][C:16]1[CH:15]=[C:14]([C@H:10]2[O:11][CH2:12][CH2:13][NH:8][CH2:9]2)[CH:19]=[CH:18][CH:17]=1

参加物

5

反応物 2

HCID 312751,4-DioxaneHCID 117871442(R)-2-(3-chlorophenyl)-morpholine-4-carboxylic acid tert-butyl ester

生成物 2

HCID 117869899(R)-2-(3-chloro-phenyl)-morpholine hydrochloride収率 100.3%HCID 117871442(R)-2-(3-chlorophenyl)-morpholine-4-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 313Hydrochloric Acid溶媒

反応条件

温度
55 °C

実験手順

(R)-2-(3-Chlorophenyl)-morpholine-4-carboxylic acid tert-butyl ester was prepared using a similar procedure as that described in Example 4 (steps b-d). (R)-2-(3-Chloro-phenyl)-morpholine-4-carboxylic acid tert-butyl ester (2.7 g, 9.07 mmol) was dissolved in HCl in dioxane (4M, 11.3 mL, 45.3 mmol) and the resulting mixture was heated at 55° C. for 2 h and then stirred at room temperature overnight. The solvent was removed by concentration in vacuo. The crude product was purified by reverse phase column chromatography (5-80% acetonitrile containing 0.1% TFA in water containing 0.1% TFA). The desired fractions were pooled and concentrated in vacuo. The product was dissolved in acetonitrile and water and 0.1 mL of concentrated HCl was added. The resultant solution was lyophilized to afford (R)-2-(3-chlorophenyl)-morpholine hydrochloride (0.71 g), as a white solid. 1H NMR (400 MHz, DEUTERIUM OXIDE) δ ppm 3.18 (dd, J=12.80, 11.54 Hz, 1H) 3.30 (dd, J=12.17, 3.89 Hz, 1H) 3.34-3.51 (m, 2H) 3.99 (ddd, J=13.11, 12.11, 2.64 Hz, 1H) 4.22 (dd, J=13.18, 3.64 Hz, 1H) 4.82 (dd, J=11.42, 2.38 Hz, 1H) 7.26-7.33 (m, 1H) 7.34-7.42 (m, 2H) 7.44 (d, J=1.76 Hz, 1H).

後処理

  1. customThe solvent was removed by concentration in vacuo
  2. customThe crude product was purified by reverse phase column chromatography (5-80% acetonitrile containing 0.1% TFA in water containing 0.1% TFA)
  3. concentrationconcentrated in vacuo
  4. dissolutionThe product was dissolved in acetonitrile
  5. additionwater and 0.1 mL of concentrated HCl was added

出典と根拠

ORDレコード
ord-18c23de87f3b4b538e8b29549afd6ef5
出典データセット
uspto-grants-2016_05
特許番号
US09353096B2

反応ノート

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