Methanol → HCID 58280450、化合物

HRID 1879476ノート

反応式

HRID 1879476 の反応式
C([O:3][C:4]([CH:6]1[CH2:10][CH2:9][S:8](=[O:12])(=[O:11])[N:7]1[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][N:21]([CH2:32][C:33]2[C:38]([Cl:39])=[CH:37][CH:36]=[C:35]([O:40][CH3:41])[C:34]=2[F:42])[C@H:22]([CH2:28][N:29]([CH3:31])[CH3:30])[CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH:15]=1)=[O:5])C.O.[OH-].[Li+].CO>O1CCCC1>[Cl:39][C:38]1[C:33]([CH2:32][N:21]([CH2:20][C:16]2[CH:15]=[C:14]([CH:19]=[CH:18][CH:17]=2)[CH2:13][N:7]2[CH:6]([C:4]([OH:5])=[O:3])[CH2:10][CH2:9][S:8]2(=[O:12])=[O:11])[C@H:22]([CH2:28][N:29]([CH3:30])[CH3:31])[CH2:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[C:34]([F:42])[C:35]([O:40][CH3:41])=[CH:36][CH:37]=1

参加物

6

反応物 4

HCID 887MethanolHCID 962WaterHCID 3939Lithium HydroxideHCID 58280466HCID 58280466、化合物

生成物 1

HCID 58280450HCID 58280450、化合物

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

2-(3-{[(6-Chloro-2-fluoro-3-methoxy-benzyl)-((S)-1-dimethylaminomethyl-3,3-dimethyl-butyl)-amino]-methyl}-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid ethyl ester (0.865 g, 1.4 mmol) was dissolved in tetrahydrofuran (5.6 mL). Water (5.6 mL) and lithium hydroxide (0.050 g, 2.07 mmol) and methanol (1.2 mL) were added. The reaction was stirred at room temperature for 2.5 hours after which the reaction was concentrated under reduced pressure. To the residue was added dichloromethane and aqueous hydrochloric acid (pH˜7) resulting in an emulsion. The reaction was then concentrated to dryness under reduced pressure. The crude material was purified by supercritical fluid chromatography into the corresponding Epimer 1 and Epimer 2 of 2-(3-{[(6-Chloro-2-fluoro-3-methoxy-benzyl)-((S)-1-dimethylaminomethyl-3,3-dimethyl-butyl)-amino]-methyl}-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid (0.084 g (Epimer 1) and 0.089 g (Epimer 2), respectively, 99% (combined yield)).

後処理

  1. concentrationwas concentrated under reduced pressure
  2. additionTo the residue was added dichloromethane and aqueous hydrochloric acid (pH˜7)
  3. customresulting in an emulsion
  4. concentrationThe reaction was then concentrated to dryness under reduced pressure
  5. customThe crude material was purified by supercritical fluid chromatography into the corresponding Epimer 1 and Epimer 2 of 2-(3-{[(6-Chloro-2-fluoro-3-methoxy-benzyl)-((S)-1-dimethylaminomethyl-3,3-dimethyl-butyl)-amino]-methyl}-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid (0.084 g (Epimer 1) and 0.089 g (Epimer 2)
  6. customrespectively, 99% (combined yield))

出典と根拠

ORDレコード
ord-e014677589b749e5bce43065a1617c9e
出典データセット
uspto-grants-2012_11
特許番号
US08314250B2

反応ノート

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