Potassium hydride → (S)-5,11-Dihydro-5-[1-(4-methoxyphenethyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]thiazepine

HRID 1460471ノート

反応式

HRID 1460471 の反応式
[H-].[K+].[CH:3]1[C:13]2[CH2:12][S:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=3[NH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.Cl[C@@H:19]1[CH2:24][CH2:23][CH2:22][N:21]([CH2:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[CH2:20]1>COCCOC>[CH3:34][O:33][C:30]1[CH:29]=[CH:28][C:27]([CH2:26][CH2:25][N:21]2[CH2:22][CH2:23][CH2:24][C@H:20]2[CH2:19][N:8]2[C:7]3[CH:6]=[CH:5][CH:4]=[CH:3][C:13]=3[CH2:12][S:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]2=3)=[CH:32][CH:31]=1

参加物

5

反応物 3

HCID 82127Potassium hydrideHCID 8269716,11-Dihydrobenzo[c][1,5]benzothiazepineHCID 15481943(R)-3-chloro-1-(4-methoxyphenethyl)piperidine

生成物 1

HCID 9824029(S)-5,11-Dihydro-5-[1-(4-methoxyphenethyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]thiazepine収率 12%

試薬・触媒・溶媒 1

HCID 80711,2-Dimethoxyethane溶媒2 回

実験手順

Potassium hydride (35% dispersion in oil, 229 mg) was added to a solution of 5,11-dihydrodibenzo[b,e][1,4]thiazepine (see U.S. Pat. No. 3,188,322 [Chem. Abs., 63, 8384h (1965)] and I. Udea and S. Umio, Bull. Chem. Soc. Japan, 48(8), 2323 (1975)) (425 mg) in DME (1,2-dimethoxyethane) (20 ml) and the mixture stirred at room temperature for 30 minutes, treated with a solution of (R)-3-chloro-1-(4-methoxyphenethyl)piperidine (see Preparation 1) (507 mg) in DME (5 ml) and heated under reflux for 18 hours. The mixture was cooled to room temperature, quenched with water and extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulphate and evaporated under reduced pressure. The residue was purified by chromatography on silica gel, performing a gradient elution using initially dichloromethane as eluant and changing to dichloromethane/saturated methanolic ammonia (98:2). The appropriate fractions were combined and evaporated under reduced pressure to give the title compound as a colourless oil, (100 mg, 12%), [α]58925 -60.9° (c=0.57 in ethanol).

後処理

  1. temperatureheated
  2. temperatureunder reflux for 18 hours
  3. customquenched with water
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with water
  6. dry with materialdried over sodium sulphate
  7. customevaporated under reduced pressure
  8. customThe residue was purified by chromatography on silica gel
  9. washa gradient elution
  10. customevaporated under reduced pressure

出典と根拠

ORDレコード
ord-d8c8e1756bf44859a3ed78fecb995213
出典データセット
uspto-grants-1991_12
特許番号
US05071844

反応ノート

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