Ethanol → 3-[1-(2,3-Dichlorophenoxy)-3-methylsulfanylpropyl]pyrrolidine

HRID 1254998ノート

反応式

HRID 1254998 の反応式
C(OC([N:8]1[CH2:12][CH2:11][CH:10]([CH:13]([OH:18])[CH2:14][CH2:15][S:16][CH3:17])[CH2:9]1)=O)(C)(C)C.[H-].[Na+].[Cl:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24](F)[C:23]=1[Cl:29].CCO>CN(C=O)C.Cl>[Cl:21][C:22]1[C:23]([Cl:29])=[CH:24][CH:25]=[CH:26][C:27]=1[O:18][CH:13]([CH:10]1[CH2:11][CH2:12][NH:8][CH2:9]1)[CH2:14][CH2:15][S:16][CH3:17]

参加物

7

反応物 4

HCID 702EthanolHCID 24758Sodium hydride2 回HCID 119011Benzene, 1,2-dichloro-3-fluoro-HCID 668597603-(1-Hydroxy-3-methylsulfanylpropyl)pyrrolidine-1-carboxylic Acid t-Butyl Ester

生成物 1

HCID 581202633-[1-(2,3-Dichlorophenoxy)-3-methylsulfanylpropyl]pyrrolidine

試薬・触媒・溶媒 2

HCID 313Hydrochloric Acid溶媒HCID 6228Dimethylformamide溶媒

実験手順

3-(1-Hydroxy-3-methylsulfanylpropyl)pyrrolidine-1-carboxylic acid t-butyl ester (49 mg, 180 mmol) was dissolved in DMF (550 μL). 60% NaH in oil (60:40, NaH:mineral oil, 8.5 mg, 210 μmol) was slowly added, and the mixture was stirred for 15 minutes at room temperature. 1,2-Dichloro-3-fluorobenzene (62 μL, 530 μmol) was added, and the resulting mixture was heated at 90° C. for 24 hours. The reaction was quenched with MeOH, and DMF/MeOH was removed in vacuo. The product was dissolved in 1.25M HCl in EtOH (1.4 mL, 1.8 mmol) and stirred overnight at room temperature. The product was then purified by preparative HPLC to yield the title compound as a mixture of all 4 stereoisomers (R,R, R,S, S,S, and S,R) as mono-TFA salts (20 mg, 100% purity). MS m/z: [M+H]+ calcd for C14H19Cl2NOS, 320.06. found 320.0.

後処理

  1. temperaturethe resulting mixture was heated at 90° C. for 24 hours
  2. customThe reaction was quenched with MeOH, and DMF/MeOH
  3. customwas removed in vacuo
  4. stirringstirred overnight at room temperature
  5. customThe product was then purified by preparative HPLC

出典と根拠

ORDレコード
ord-f292b0e4231d40778223fddf3fe3aa8c
出典データセット
uspto-grants-2013_06
特許番号
US08455665B2

反応ノート

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